1. Academic Validation
  2. SRT2183 impairs ovarian cancer by facilitating autophagy

SRT2183 impairs ovarian cancer by facilitating autophagy

  • Aging (Albany NY). 2020 Nov 20;12(23):24208-24218. doi: 10.18632/aging.104126.
Tingting Sun 1 Yanfen Hu 2 Weipeng He 1 Yuru Shang 3 Xiaohong Yang 4 Liyun Gong 4 Xianbin Zhang 5 6 7 Peng Gong 5 7 Guofen Yang 1
Affiliations

Affiliations

  • 1 Department of Gynecology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
  • 2 Discovery Department, Elpiscience Biopharma Ltd., Shanghai 201203, China.
  • 3 Department of Plastic Surgery, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, Shenzhen 518055, China.
  • 4 Department of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen 518060, China.
  • 5 Department of General Surgery and Carson International Cancer Research Center, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, Shenzhen 518055, China.
  • 6 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China.
  • 7 Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen 518060, China.
Abstract

The 5-year survival rate of ovarian Cancer patients is only 47%, and developing novel drugs for ovarian Cancer is needed. Herein, we evaluated if and how SRT2183, a sirtuin-1 activator, impairs the ovarian Cancer cells. OVCAR-3 and A2780 cells were treated with SRT2183. Cell viability was measured by cell counting kit-8 assay and clonogenic assay. Apoptosis was determined by flow cytometry with Annexin V and propidium iodide. The level of Autophagy was evaluated by western blot and immunofluorescence. The activities of Akt/mTOR/70s6k and MAPK signaling pathway were measured by immunoblot. SRT2183 inhibited the growth of ovarian Cancer cells, increased the accumulation of Bax, cleaved-caspase 3 and cleaved-PARP, and decreased the level of anti-apoptotic Bcl-2 and Mcl-1. SRT2183 increased the LC3II level, and enhanced the degradation of p62/SQSTM1. SRT2183 increased the formation of GFP-LC3 puncta and induced the maturation of autophagosome. Interestingly, knockdown of Autophagy related 5 and 7 significantly impaired the anti-carcinoma activity of SRT2183, implying that SRT2183 impaired the ovarian Cancer cells by inducing Autophagy. SRT2183 decreased the accumulation of p-Akt, p-mTOR and p-70s6k, and activated the p38 MAPK signaling pathway. This indicated that Akt/mTOR/70s6k and p38 MAPK signaling pathway might be involved in the SRT2183-mediated Autophagy and Apoptosis.

Keywords

AKT/mTOR pathway; STR2183; apoptosis; autophagy; p38 MAPK pathway.

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