J Cancer 2018; 9(22):4150-4155. doi:10.7150/jca.26948

Research Paper

Niclosamide Inhibits Cell Growth and Enhances Drug Sensitivity of Hepatocellular Carcinoma Cells via STAT3 Signaling Pathway

Chengzhi Wang1,4, Xiaoqing Zhou2, Hongjuan Xu1, Xiaqing Shi1, Jinfeng Zhao1, Manyi Yang1, Lihua Zhang1, Xin Jin1, Yu Hu3, Xia Li4, Xiangcheng Xiao4, Mingmei Liao1✉

1. Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.
2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
3. Center for Experimental Medical Research, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, P.R. China
4. Department of Nephrology, Xiangya Hospital,Central South University, Changsha, Hunan, 410008, P.R. China

Abstract

Aims: Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor worldwide, with a high mortality rate at advanced stages. In this study, we investigated the effect of niclosamide on cell growth and drug sensitivity in human HCC and elucidated the underlying mechanism.

Methods: Three human HCC cell lines (HepG2, QGY-7703 and SMMC-7721) were used to evaluate the effect of niclosamide. Cell proliferation was measured by MTT assay and colony formation assay. Assessment of apoptosis was evaluated by flow cytometry and Hoechst staining. The mRNA and protein levels were analyzed by real-time PCR and western blot, respectively.

Results: Niclosamide suppressed cell viability, inhibited clone formation, and induced cell apoptosis in HCC cells dose- and time-dependently. Furthermore, niclosamide synergized with cisplatin to promote the apoptosis of HCC cells. With niclosamide treatment, phospho-STAT3 (Y705) was inactivated and the downstream antiapoptotic proteins Mcl-1 and survivin were downregulated at both mRNA and protein levels in HCC cells.

Conclusion: Niclosamide has effective function in anti-HCC and may be a single or combined drug treatment for HCC and acts via the STAT3 signaling pathway.

Keywords: Niclosamide, Cell growth, Drug sensitivity, STAT3 signaling, Mcl-1, Hepatocellular carcinoma

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How to cite this article:
Wang C, Zhou X, Xu H, Shi X, Zhao J, Yang M, Zhang L, Jin X, Hu Y, Li X, Xiao X, Liao M. Niclosamide Inhibits Cell Growth and Enhances Drug Sensitivity of Hepatocellular Carcinoma Cells via STAT3 Signaling Pathway. J Cancer 2018; 9(22):4150-4155. doi:10.7150/jca.26948. Available from http://www.jcancer.org/v09p4150.htm