چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| نرگس رستمی | اول |
| فرهاد جدیدی نیارق | دوم |
| افشین نیک خو | سوم |
| علی مسجدی | چهارم |
| فاطمه اطیابی | پنجم |
| علی رستگاری | ششم |
| ویدا هاشمی | هشتم |
| شیما بستاکی | نهم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Silencing S1PR1 and GP130 in 4T1 breast cancer cells and B16F10 melanoma cancer cells through siRNA-loaded trimethyl chitosan nanoparticles Narges Rostami1,2, Farhad Jadidi iaragh1,2,3, Afshin Nikkhoo1,2, Ali Masjedi1,2, Fatemeh Atyabi4,5 , Ali Rastegari4, Masoomeh Baghaei5 , Vida Hashemi6,1,2, Shima Bastaki7,1 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 4. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran 5. Nanotechnology Research Center , Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran 6. Department of Basic Sciences, Faculty of Medicine, Maragheh University of Medical Sciences, Maragheh, Iran 7. Department of Cellular and Molecular Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran Background: There are several stimulating molecules in tumor microenvironment which enhance tumor growth. Among them, S1PR1 promotes cancer cell survival, invasion, metastasis and radio/chemo-resistance in various cancers via JAK/STAT3 and other signaling pathways. Glycoprotein130 is a shared subunit of IL-6 receptor which mediates tumor progression following ligation with IL-6 on tumor cells. IL-6 via its receptor, gp130, triggers STAT3 stimulation. There is an amplification loop between S1PR1 and IL-6 for stimulation of STAT3 signaling in tumor cells. Therefore combinatorial blockage of these molecules can be considered as an effective immunotherapeutic approach for cancer therapy. Methods: S1PR1-siRNA and gp130-siRNA were encapsulated into trimethyl chitosan (TMC) nanoparticles (NPs) were generated through ionic gelation of TMC by hyaloronic acid and employed to suppress the expression of S1PR1 and gp130 molecules on 4T1 and B16F10 cancer cells, in vitro. All of physicochemical characteristics, serum stability, siRNA loading efficiency, siRNA release pattern, and cellular uptake of NPs were assessed. The expression of target genes was evaluated by real-time PCR. Anti-proliferative effect of nanoformulation was assessed by MTT assay. Wound healing assay was performed to assay anti-metastatic effects. Results: SiRNA-loaded NPs had about 100 nm size with a polydispersive index below 0.3 and a zeta potential about 15. Generated NPs exhibited high siRNA loading capacity, high serum stability, and efficiently uptaken by cancer cells. The NPs demonstrated low toxic effect during 72 hr cell culture. In addition, S1PR1-siRNA and gp130-siRNA-loaded TMC NPs could efficiently suppress the expression of S1PR1 and gp130. Combination treatment of tumor cells also led to downregulation of anti-apoptotic proteins, angiogenic, and metastatic molecules. Suppression of S1PR1 and gp130 was also associated with decreased migration of cancer cells. Conclusion: Combinatorial treatment of tumor cells with S1PR1-siRNA and gp130-siRNA-loaded TMC NPs may be considered as a promising therapeutic tool for cancer therapy. |
| کلمات کلیدی | Key words: S1PR1, gp130, cancer immunotherapy, Trimethyl chitosan |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| NargesRostami-Abstract (1).docx | 1397/09/11 | 15471 | دانلود |
| abstract pic.jpg | 1397/09/11 | 137326 | دانلود |
| abstract pic 2.jpg | 1397/09/11 | 137515 | دانلود |
| safheye aval.jpg | 1397/09/11 | 105226 | دانلود |
| pasokh be virayesh.docx | 1397/09/11 | 11813 | دانلود |
| participation.pdf | 1397/08/09 | 1400625 | دانلود |
| poster.pdf | 1397/08/09 | 1323395 | دانلود |
| abstract.jpg | 1397/08/09 | 91591 | دانلود |
| 2a.docx | 1397/08/09 | 15960 | دانلود |
| 1a.docx | 1397/08/09 | 14448 | دانلود |
