title: Knockdown of autophagy-related gene LC3 enhances the sensitivity of HepG2cells to epirubicin.
abstract: Hepatocellular carcinoma (HCC) is a major public health problem. Despite new chemotherapeutic treatments, drug resistance remains a major clinical obstacle to successful treatment in HCC patients. Therefore, novel therapeutic targets and new modalities of treatment are urgently required. In this study, tetracycline-inducible lentivirus-mediated RNA interference (RNAi) was employed to knock down microtubule-associated protein 1 light chain 3 (LC3) gene, which encodes a key protein in the induction of autophagy, to study the protective function of autophagy in liver cancer tolerant to epirubicin. The effect of combined treatment with lentiviral shLC3 and epirubicin on cell growth and chemosensitivity to epirubicin in the HCC cell line HepG2were also investigated. The results demonstrated that lentivirus-mediated LC3 silencing significantly inhibited cell proliferation. In addition, combined treatment with lentiviral shLC3 and epirubicin significantly decreased the survival rate of HepG2cells, compared with that following treatment with either agent alone. Overall, the results from this study suggest for the first time, to the best of our knowledge, that LC3 plays a key role in HCC tumorigenesis, and is a novel therapeutic target for HCC.
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wanxin
authors.initials: W
authors.lastname: Peng
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: DU
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Fengyi
authors.initials: F
authors.lastname: DU
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
keywords: autophagy; chemoresistance; hepatocellular carcinoma; lentivirus; light chain 3