1. Combination of HSP90 and autophagy inhibitors promotes hepatocellular carcinoma apoptosis following incomplete thermal ablation.
- Author
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Chen, Fen, Xie, Haiyang, Bao, Haiwei, Violetta, Laurencia, and Zheng, Shusen
- Subjects
HEPATOCELLULAR carcinoma ,HEAT shock proteins ,LASER ablation ,APOPTOSIS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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