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Updated: Nov 29, 2025
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
SRT2183 impairs ovarian cancer by facilitating autophagy
Tingting Sun1, Yanfen Hu2, Weipeng He1
1Department of Gynecology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, 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.
Insights
SRT2183, a sirtuin-1 activator, inhibits ovarian cancer cell growth by inducing apoptosis and autophagy. This novel drug candidate shows promise for treating ovarian cancer by targeting key cellular pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ovarian cancer has a poor 5-year survival rate (47%), necessitating new therapeutic strategies.
- Sirtuin-1 (SIRT1) activators are being explored for their potential in cancer treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of SRT2183, a SIRT1 activator, on ovarian cancer cells.
- To elucidate the mechanisms underlying SRT2183's action, including its impact on apoptosis and autophagy.
Main Methods:
- Ovarian cancer cell lines (OVCAR-3, A2780) were treated with SRT2183.
- Cell viability, apoptosis, autophagy, and signaling pathway activation (AKT/mTOR/70s6k, MAPK) were assessed using various assays (CCK-8, clonogenic, flow cytometry, Western blot, immunofluorescence).
Main Results:
- SRT2183 significantly inhibited ovarian cancer cell growth and induced apoptosis by altering BAX, cleaved-caspase 3, cleaved-PARP, Bcl-2, and Mcl-1 levels.
- SRT2183 promoted autophagy, evidenced by increased LC3II, p62/SQSTM1 degradation, and autophagosome maturation.
- Knockdown of autophagy-related genes impaired SRT2183's anti-cancer effects, confirming autophagy's role.
- SRT2183 modulated the AKT/mTOR/70s6k pathway (decreasing activity) and activated the p38 MAPK pathway.
Conclusions:
- SRT2183 demonstrates potent anti-ovarian cancer activity by inducing both apoptosis and autophagy.
- The findings suggest that SRT2183's efficacy involves the modulation of AKT/mTOR/70s6k and p38 MAPK signaling pathways.
- SRT2183 represents a potential therapeutic agent for ovarian cancer, warranting further investigation.
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