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Int. J. Mol. Sci. 2013, 14(12), 23212-23230; doi:10.3390/ijms141223212
Article

Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

1
, 2
, 1,2,*  and 1
Received: 17 September 2013; in revised form: 12 November 2013 / Accepted: 14 November 2013 / Published: 25 November 2013
(This article belongs to the Section Molecular Pathology)
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Abstract: Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.
Keywords: matrine; hepatocellular carcinoma; autophagy; apoptosis; autophagic inhibitor; chloroquine matrine; hepatocellular carcinoma; autophagy; apoptosis; autophagic inhibitor; chloroquine
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wang, L.; Gao, C.; Yao, S.; Xie, B. Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells. Int. J. Mol. Sci. 2013, 14, 23212-23230.

AMA Style

Wang L, Gao C, Yao S, Xie B. Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells. International Journal of Molecular Sciences. 2013; 14(12):23212-23230.

Chicago/Turabian Style

Wang, Li; Gao, Chun; Yao, Shukun; Xie, Bushan. 2013. "Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells." Int. J. Mol. Sci. 14, no. 12: 23212-23230.


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