other ارزیابی اثرهای ضدسرطانی پپتید ملیتین بر ردۀ‌ سلولی سرطان ریه در شرایط برون‌تنی سلولی و مولکولی Cellular and molecular مقاله پژوهشی Research Article <span style="font-size:11pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:">سابقه و هدف: </span></span></b><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:">بیماران مبتلا به سرطان ریه از نوع سلول‌های سرطانیِ سلول غیرکوچک (</span></span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">NSCLC</span></span><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:">) دارای پیش‌آگهی پایین بوده و درمان‌های موجود دارای اثرهای جانبی زیادی برای آن‌ها می‌باشد. از طرفی تعداد زیادی از مطالعه‌های اخیر به اثرهای ضدسرطانی پپتید ملیتین پرداخته‌اند. هدف ما از این مطالعه بررسی اثرهای ضدسرطانی ملیتین بر سلول‌های </span></span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Calu-3</span></span><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:"> سرطان ریه می‌باشد.</span></span><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span b="" nazanin="" style="font-family:">مواد و روش&shy; ها: </span></span></b><span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">میزان</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">کشندگی</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">توسط</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">ملیتین</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">بر</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">روی</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">دو</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">ردۀ</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">سلولی</span></span></span></span> <span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> و</span></span></span></span> <span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MRC5</span></span></span></span><span style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> (به</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">‌</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">عنوان</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">سلول</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">نرمال) با</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">استفاده</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">از</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">آزمون</span></span></span></span> <span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MTT</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> موردارزیابی</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">قرار</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">گرفت. از</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">روش</span></span></span></span> <span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Real-Time PCR</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> برای</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">مشخص</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">شدن</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">بیان</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">‌</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">ژن</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">‌</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">های</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">دخیل</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">در</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">فرآیند</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">آپوپتوز</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">شامل</span></span></span></span> <i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">BAX</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">، </span></span></span></span>&nbsp;<i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">BCL2</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">و</span></span></span></span> <i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">CASP3</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> استفاده</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">گردید. در</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">نهایت</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">به</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">‌</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">منظور</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">بررسی</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">نقش</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">مهاری</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">ملیتین</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">بر</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">فرآیند</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">مهاجرت</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">سلولی،</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">از</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">روش</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">آزمون ارزیابی مهاجرت سلولی استفاده</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">شده</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">‌</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">است.</span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">یافته‌ها:</span></span></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> میزان 50% کشندگی (</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">IC₅₀</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">) برای ملیتین برای دو ردۀ سلولی </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> و </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MRC5</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> به‌ترتیب </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">&mu;g/mL</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">67/1 و </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">&mu;g/mL</span></span></span></span> <span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">44/3 در 24 ساعت به‌دست آمد. میزان بیان‌ژن‌های </span></span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">BAX</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> و </span></span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">CASP3</span></span></span></span></i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> در سلول‌های</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3 </span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">،</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">82/2 و 31/4 برابر و در سلول‌های</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MRC5 </span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">،</span></span></span></span> <span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">58/1 و 07/4 برابر افزایش پیدا کرد، از طرف دیگر بیان‌ژن </span></span></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">BCL2</span></span></span></span></i><i> </i><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">در سلول‌های</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3 </span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">&nbsp;35/0 برابر و در سلول‌های</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MRC5 </span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">&nbsp;64/0 برابر نسبت به گروه تیمارنشده کاهش‌یافتپ. </span></span></span></span><span lang="AR-SA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">به‌علاوه نتایح حاصل از آزمون ارزیابی مهاجرت سلولی نشان‌دهندۀ مهار فرآیند مهاجرت سلولی توسط ملیتین بود.</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:Calibri,sans-serif"><b><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">نتیجه‌گیری</span></span></span></span></b><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black">: ملیتین اثرات ضدسرطانی بر روی ردۀ سلولی </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> سرطان ریه نشان می‌دهد. به‌علاوه ملیتین می‌تواند موجب القای آپوپتوز و مهار مهاجرت سلولی در سلول‌های سرطانی ریه گردد. ملیتین با افزایش بیان‌ژن‌های مؤثر در فرآیند آپوپتوز باعث حرکت سلول‌ها به سمت مرگ سلولی می‌گردد. علاوه‌بر این با توجه به مقایسۀ نتایج به‌دست‌آمده از اثرهای ملیتین بر ردۀ سلول سرطانی </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">Calu-3</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> با ردۀ سلول سالم </span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times=""><span style="color:black">MRC5</span></span></span></span><span lang="FA" style="font-size:12.0pt"><span style="background:white"><span b="" nazanin="" style="font-family:"><span style="color:black"> می‌توان نتیجه گرفت که اثرگذاری این پپتید بر سلول‌های سرطانی به‌میزان بالاتر و در دوزهای پایین‌تری صورت می‌گیرد.</span></span></span></span></span></span></span></span> <span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Aim and Background: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Non</span></span><span style="font-size:10.0pt"><span mincho="" ms="" style="font-family:">‑</span></span><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">small cell lung cancer (NSCLC) patients have a frequently poor prognosis and current therapies have large side effects. Numerous studies have been focused on the anti-cancer effects of melittin. Concerning the anti-cancer effects of melittin, this study aimed to evaluate melittin&#39;s anti-cancer effects on Calu-3 lung cancer cell line.</span></span></span></span><br> <span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Material and Methods: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Cytotoxicity of melittin on Calu-3 and MRC5 cells was assessed using MTT assay. Real-Time PCR was used to determine expression of apoptotic and pro-apoptotic <i>BAX</i>, <i>BCL2</i>, and <i>CASP3</i> genes. Furthermore, a wound healing assay was performed to compare the inhibition effects of melittin on the migration of interested cells. </span></span></span></span><br> <span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Results: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">IC₅₀ values of melittin for Calu-3 and MRC5 were respectively 1.67&mu;g/mL and 3.44&mu;g/mL after 24h. Expression levels of <i>BAX</i> and <i>CASP3</i> increased &lsquo;2.82 and 4.31&rsquo; and &lsquo;1.58 and 4.07&rsquo; fold in Calu-3 and MRC5, whereas <i>BCL2</i> gene expression decreased 0.64 and 0.35-fold in the mentioned cell lines. It is demonstrated that cell migration is inhibited by melittin.</span></span></span></span><br> <span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Conclusion: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Melittin has an anti-cancer effect on Calu-3 lung cancer cell line. Furthermore, melittin induces apoptosis and inhibits cell migration of lung cancer cells. Melittin increases the apoptotic gene expression level and eventually causes the cells to move toward cell death. In addition, comparing the effects of melittin on Calu-3 cancer cells and MRC5 normal cells, it can be concluded that melittin has inhibitory and apoptotic effects on cancer cells at lower doses.</span></span></span></span><br> <br> &nbsp; NSCLC, ملیتین, آپوپتوز, BAX , BCL2,CASP3. NSCLC, Melittin, apoptosis, BAX, BCL2, CASP3. 57 68 http://ncmbjpiau.ir/browse.php?a_code=A-10-1936-2&slc_lang=other&sid=1 Pooyan Honari پویان هنری 100319475328460014916 100319475328460014916 No Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University. Tehran, Iran. گروه زیست‌شناسی سلولی‌ومولکولی، دانشکدۀ علوم‌وفناوری‌های همگرا، دانشگاه آزاد اسلامی واحد علوم و تحقیقات، تهران، ایران Delavar Shahbazzadeh دلاور شهباز زاده 100319475328460014917 100319475328460014917 No Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran. Tehran, Iran آزمایشگاه ونوم، بخش بیوتکنولوژی انستیتو پاستور، تهران، ایران Mahdi Behdani مهدی بهدانی 100319475328460014918 100319475328460014918 No Kamran Pooshang Bagheri کامران پوشنگ باقری kamranpb@gmail.com 100319475328460014919 100319475328460014919 Yes Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Dept., Biotechnology Research Center, Pasteur Institute of Iran. Tehran, Iran آزمایشگاه ونوم، بخش بیوتکنولوژی انستیتو پاستور، تهران، ایران