Effect of CCR4 on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mice

Abstract

Objective To investigate the effect of CC chemokine receptor 4(CCR4) on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mouse models. Methods Western blot was used to detect the expression of CCR4 in hepatocellular carcinoma cell line. Lentivirus was utilized to construct PLC/PRF/5 and SMMC-7721 cell lines stably overexpressing and silencing CCR4, which were verified by Western blot. The influence of CCR4 on the radiosensitivity of hepatocellular carcinoma cells was assessed by plate clone formation assay. The effect of CCR4 on the tumorigenesis in hepatocellular carcinoma cells in vivo was evaluated by tumorigenesis assay in nude mice. Results CCR4 was highly expressed in highly-metastatic hepatocellular carcinoma cells and lowly expressed in hepatocellular carcinoma cells with low metastases. The PLC/PRF/5 and SMMC-7721 cells, which stably overexpressed and silenced CCR4, were successfully established. Overexpression of CCR4 reversed the inhibitory effect of sorafenib radiotherapy on PLC/PEF/5, whereas knockdown of CCR4 could increase the radiosensitivity of SMMC-7721 to sorafenib. Overexpressing CCR4 could promote the tumorigenicity of PLC/PEF/5, whereas knockdown of CCR4 could inhibit the tumorigenicity of SMMC-7721 in nude mice. Conclusion CCR4 overexpression significantly reduces the radiosensitivity of PLC/PRF/5 and increases the tumorigenicity in nude mice, whereas knockdown of CCR4 considerably increases the chemosensitivity and radiosensitivity of SMMC-7721 and suppresses the tumorigenicity in nude mice. Key words: Chemokine receptor; Sorafenib; irradiation; Hepatocellular carcinoma cell line; Nude mice