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Combination of HSP90 and autophagy inhibitors promotes hepatocellular carcinoma apoptosis following incomplete thermal ablation.
- Source :
-
Molecular Medicine Reports . Jul2020, Vol. 22 Issue 1, p337-343. 7p. - Publication Year :
- 2020
-
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]
- Subjects :
- *HEPATOCELLULAR carcinoma
*HEAT shock proteins
*LASER ablation
*APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 17912997
- Volume :
- 22
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Molecular Medicine Reports
- Publication Type :
- Academic Journal
- Accession number :
- 143609702
- Full Text :
- https://doi.org/10.3892/mmr.2020.11080