期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 143, 期 3, 页码 219-225出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2020.04.006
关键词
CCND1; RAD51; Liver cancer stem cell; 5-Fluorouracil; Hepatocellular carcinoma
资金
- Natural Science Foundation of Jiangxi Province [20151BAB205100]
Objective: Chemoresistance is one of the major barriers in chemotherapy-based hepatocellular carcinoma (HCC) intervention. 5-Fluorouracil (5-Fu) is a widely used as an anticancer drug. Liver cancer stem cells (LCSCs) are considered the origin of tumor recurrence and resistance. CCND1 (Cyclin D1) plays an important role in tumorigenesis and metastasis in multiple cancers including HCC. Herein, this study was designed to explore the role of CCND1 in regulating LCSCs differentiation and 5-Fu resistance in HCC cells. Methods: The CCND1 mRNA level was examined by qRT-PCR. The protein levels of gamma-H2AX (a DNA damage marker) and RAD51 (a DNA repair protein) were examined by Western blot. CD133 was used as a LCSC marker and CD133+ cell percentage in HCC cells was detected by flow cytometry. Results: CCND1 silencing decreased CD133+ cell percentage in HepG2 and SMMC-7721 cells. Furthermore, CCND1 silencing significantly increased protein level of gamma-H2AX and decreased that of RAD51 under 5-Fu exposure. Moreover, CCND1 silencing enhanced the sensitivity of HepG2 and SMMC-7721 cells to 5-Fu, which was effectively abrogated by RAD51 upregulation. Conclusion: Collectively, CCND1 silencing suppresses LCSCs differentiation and overcomes 5-Fu resistance in HCC. (C) 2020 The Authors. Production and hosting by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据