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Int. J. Mol. Sci. 2016, 17(4), 610; doi:10.3390/ijms17040610

Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT

Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei, China
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Academic Editor: Johannes Haybaeck
Received: 29 March 2016 / Revised: 13 April 2016 / Accepted: 18 April 2016 / Published: 22 April 2016
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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Abstract

Background: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. Methods: The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models. Non-smad signaling was detected by Western blotting to search for the underlying mechanisms. Results: Smad3 enhanced the chemosensitivity of HCC cells to cisplatin. Smad3 upregulated p21Waf1/Cip1 and downregulated c-myc and bcl2 with the treatment of cisplatin. Moreover, overexpression of smad3 repressed the phosphorylation of AKT, and vice versa. Inhibition of PI3K/AKT pathway by LY294002 restored chemosensitivity of smad3-deficiency cells to cisplatin in HCC. Conclusion: Smad3 sensitizes HCC cells to the effects of cisplatin by repressing phosphorylation of AKT and combination of inhibitor of AKT pathway and conventional chemotherapy may be a potential way to solve drug resistance in HCC. View Full-Text
Keywords: hepatocelluar carcinoma; smad3; AKT; drug resistance; cisplatin; LY294002 hepatocelluar carcinoma; smad3; AKT; drug resistance; cisplatin; LY294002
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. (CC BY 4.0).

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Zhou, H.-H.; Chen, L.; Liang, H.-F.; Li, G.-Z.; Zhang, B.-X.; Chen, X.-P. Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT. Int. J. Mol. Sci. 2016, 17, 610.

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