Autophagy as a Regulator of Cell Fate in Statin Targeting of Rhabdomyosarcoma

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 373

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شناسه ملی سند علمی:

NSCMRMED03_024

تاریخ نمایه سازی: 30 دی 1397

چکیده مقاله:

Rhabdomyosarcoma (RMS) which is both occurred in children and adultsis an aggressive soft-tissue malignant tumor. Soft tissue sarcomas accountfor approximately 1% of all cancers and 10% of all childhood cancersand it is worth mentioning that RMS comprises 50% of all childhoodsoft tissue sarcomas. Based on clinical reports, survival among patientswith metastatic RMS has not significantly improved in the past fewyears, emphasizing an urgent for developing new strategies to treat andprevent this disease. Statins are inhibitors of mevalonate (MEV) cascadewhich is involved in producing prenylation intermediates (geranylgeranylpyrophosphate [GGPP], and farnesyl pyrophosphate [FPP]). In the pastfew years, there are several clinical and basic science reports focusing onthe anti-cancer effect of statins. In the current work we have used humanrhabdomyosarcoma cell line (RH30) (Human muscle cancer cells) andmouse muscle cell line (C2C12) to investigate the mechanism of celldeath which is induced by MEV cascade inhibitor (Simvastatin:Simva).Our results showed that statin induces apoptotic cell death in both RH30and C2C12 cells, which is depended on FPP and GGPP. Our results alsoshowed that Simva induce differentially autophagy hallmarks in RH30and C2C12 cells and Simva-induced apoptosis is regulated via theautophagy pathway in these cells. Our 3-dimensional (3D) RH30 andC2C12 model also showed that Simva. induced cell death involves bothapoptosis and autophagy mechanism in 3D culture model.Funding Agency: Saeid Ghavami and Shala Shojaei were supported byHealth Science Foundation general operating grant. Shahla Shojaei wasalso supported by Mitacs Accelerate PDF. Saeid Ghavami and Joseph WGordon were also supported by CHRIM operating grant. Simone da SilvaRosa was supported by UMGF studentship. Mohsen Akbari and EhsanSamie thank NSERC (Discovery program) and BC Cancer Foundation fortheir financial support. Mohsen Akbari also thanks Canadian Foundationfor Innovations and B.C. Knowledge Development Fund for supportingthis project.

نویسندگان

Arya Emami

Department of Human Anatomy and Cell Science, Rady Faculty of Health Science, University of Manitoba, Winnipeg, Canada

Shahla Shojaei

Department of Human Anatomy and Cell Science, Rady Faculty of Health Science, University of Manitoba, Winnipeg, Canada- Laboratory for Innovation in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, ۳۸۰۰ Finnerty Rd.,

Ehsan Samie

Laboratory for Innovation in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, ۳۸۰۰ Finnerty Rd., Victoria, BC, Canada V۸P ۲C۵; Center for Biomedical Research, University of Victoria, Victoria, Canada

Simone da Silva Rosa

Department of Human Anatomy and Cell Science, Rady Faculty of Health Science, University of Manitoba, Winnipeg, Canada- Children Hospital Research Institute of Manitoba, the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM)Theme, Universit