Inhibition of autophagy signiﬁcantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells.

Autor:	Yuan H; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Li AJ; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Ma SL; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Cui LJ; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Wu B; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Yin L; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China., Wu MC; Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2 Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
Jazyk:	angličtina
Zdroj:	World journal of gastroenterology [World J Gastroenterol] 2014 May 07; Vol. 20 (17), pp. 4953-62.
DOI:	10.3748/wjg.v20.i17.4953
Abstrakt:	Aim: To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors (HDACIs) can sensitize hepatocellular carcinoma (HCC) cells to sorafenib treatment. Methods: Bax, Bcl-2, ATG5-ATG12, p21, and p27 protein levels in Hep3B, HepG2, and PLC/PRF/5 cells were examined by Western blot. CCK8 and a fluorometric caspase-3 assay were used to examine cellular viability and apoptosis levels. The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B, HepG2, and PLC/PRF/5 cells. Results: Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth. Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations. Western blot data indicated that HDACIs and Beclin-1 knockdown increased the p53 acetylation level. The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib. Conclusion: HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1.
Databáze:	MEDLINE
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