Combination of HSP90 and autophagy inhibitors promotes hepatocellular carcinoma apoptosis following incomplete thermal ablation
- Fen Chen
- Haiyang Xie
- Haiwei Bao
- Laurencia Violetta
- Shusen Zheng
Affiliations: Department of Ultrasound, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310002, P.R. China, Key Laboratory of Combined Multi‑organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310002, P.R. China, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Zhejiang University, Hangzhou, Zhejiang 310002, P.R. China, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310002, P.R. China
- Published online on: April 21, 2020 https://doi.org/10.3892/mmr.2020.11080
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The present study evaluated the effect of combining inhibitors (17‑AAG) of heat shock protein 90 (HSP90) and autophagy (3‑MA) on apoptosis using an incomplete thermal ablation animal model. A total of 28 orthotopic mice with hepatocellular carcinoma were randomly divided into 4 groups to receive different drug interventions. Following palliative laser ablation, changes in autophagy, apoptosis and Akt/mTOR expression levels were assessed in tumors. Compared with the controls, the 17‑AAG‑treated mice exhibited significantly decreased expression levels of phosphorylated (p)‑Akt and p‑mTOR with enhanced autophagy and apoptosis; no marked increases in the expression levels of p‑Akt and p‑mTOR were observed in the 3‑MA‑treated mice, with no significant changes in autophagy; however, apoptosis was enhanced. No significant decreases in p‑Akt and p‑mTOR or any increase in autophagy were observed in the mice receiving a combination of 17‑AAG and 3‑MA, but they did exhibit a marked increase in apoptosis. Compared with 17‑AAG alone, the combination of 17‑AAG and 3‑MA resulted in a marked increase in apoptosis without enhanced autophagy. In the incomplete ablation model, the effects of autophagy and apoptosis are antagonistic. The combined use of 17‑AAG and 3‑MA can significantly promote apoptosis and is worthy of further study.