- 作者: Sheng-Tang Wu, Guang-Huan Sun, Tai-Lung Cha, Chien-Chang Kao, Sun-Yran Chang, Sheng-Chu Kuo and Tzong-Der Way
- 作者服務機構: 1. Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center 2. School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan 3. Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan R.O.C.
- 中文摘要: --
- 英文摘要:
Background
Triple-negative breast cancer (TNBC) lacks specific therapeutic target and limits to chemotherapy and is essential to develop novel therapeutic regimens. Increasing studies indicated that tamoxifen, a selective estrogen receptor modulators (SERMs), has anti-tumor therapeutic effect in estrogen receptor α (ERα)-negative tumor. Here, we determined whether autophagy was activated by tamoxifen in TNBC cells. Moreover, CSC-3436 displayed strong and selective growth inhibition on cancer cells. Next, we investigated the anti-proliferation effect of combination of CSC-3436 plus tamoxifen on cell death in TNBC cells.
Results
Our study found that tamoxifen induces autophagy in TNBC cells. Endoplasmic reticulum stress and AMPK/mTOR contributed tamoxifen-induced autophagy. Interestingly, in combination treatment with CSC-3436 enhanced the anti-proliferative effect of tamoxifen. We found that CSC-3436 switched tamoxifen-induced autophagy to apoptosis via cleavage of ATG-5. Moreover, AMPK/mTOR pathway may involve in CSC-3436 switched tamoxifen-induced autophagy to apoptosis. The combination of tamoxifen and CSC-3436 produced stronger tumor growth inhibition compared with CSC-3436 or tamoxifen alone treatments in vivo.
Conclusion
These data indicated that CSC-3436 combined with tamoxifen may be a potential approach for treatment TNBC. - 中文關鍵字: --
- 英文關鍵字: Triple-negative breast cancer, Tamoxifen, CSC-3436, Endoplasmic reticulum stress, AMPK/mTOR