AbstractObjective 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.
Fund:National Natural Science Foundation of China (u1204818)
About author:: National Natural Science Foundation of China (u1204818)
Cite this article:
Wang Wei,Ke Shanbao,Liu Mingbo et al. Effect of CCR4 on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mice[J]. Chinese Journal of Radiation Oncology, 2019, 28(2): 136-139.
Wang Wei,Ke Shanbao,Liu Mingbo et al. Effect of CCR4 on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mice[J]. Chinese Journal of Radiation Oncology, 2019, 28(2): 136-139.
[1] Galmiche A,Chauffert B,Barbare JC.New biological perspectives for the improvement of the efficacy of sorafenib in hepatocellular carcinoma[J].Cancer Lett,2014,346(2):159-162.DOI:10.1016/j.canlet.2013.12.028. [2] Whittaker S,Marais R,Zhu AX.The role of signaling pathways in the development and treatment of hepatocellular carcinoma[J].Oncogene,2010,29(36):4989-5005.DOI:10.1038/onc.2010.236. [3] Wilhelm S,Carter C,Lynch M,et al. Discovery and development of sorafenib:a multikinase inhibitor for treating cancer[J].Nat Rev Drug Discov,2006,5(10):835-844.DOI:10.1038/nrd2130. [4] Zheng M,Xu H,Liao XH,et al. Inhibition of the prolyl isomerase Pin1 enhances the ability of sorafenib to induce cell death and inhibit tumor growth in hepatocellular carcinoma[J].Oncotarget,2017,8(18):29771-29784.DOI:10.18632/oncotarget.15967. [5] Panda S,Padhiary SK,Routray S.Chemokines accentuatingprotumoral activities in oral cancer microenvironment possess anmperious stratagem for therapeutic resolutions[J].Oral Oncol,2016,60(1):8-17.DOI:10.1016/j.oraloncology.2016.06.008. [6] Chen L,Fan J,Chen H,et al. The IL-8/CXCR1 axis is associated with cancer stem cell-like properties and correlates with clinical prognosis in human pancreatic cancer cases[J].Sci Rep,2014,4(?):5911.DOI:10.1038/srep05911. [7] Du P,Liu Y,Ren H,et al. Expression of chemokine receptor CCR7 is a negative prognostic factor for patients with gastric cancer:a meta-analysis[J].Int Gastric Cancer,2017,20(2):1-11.DOI:10.1007/s10120-016-0602-8. [8] Guan G,Lu Y,Zhu X,et al. CXCR4-targeted near-infrared imaging allows detection of orthotopic and metastatic human osteosarcoma in a mouse model[J].Sci Rep,2015,5:15244.DOI:10.1038/srep15244. [9] Yu KD,Wang X,Yang C,et al. Host genotype and tumor phenotype of chemokine decoy receptors integrally affect breast cancer relapse[J].Oncotarget,2015,6(28):26519-26527.DOI:10.18632/oncotarget.4470. [10] Yang P,Li QJ,Feng Y,et al. TGF-beta-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma[J].Cancer Cell,2012,22(3):291-303.DOI:10.1016/j.ccr.2012.07.023. [11] Cheng X,Wu H,Jin ZJ,et al. Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior[J].Sci Rep,2017, 7(1):12362.DOI:10.1038/s41598-017-10267-4. [12] 刘鹏,朱远.肝细胞肝癌放疗的研究进展[J].肿瘤基础与临床,2015,(4):365-368.DOI:10.3969/j.issn.1673-5412.2015.04.037. Liu P,Zu Y.Advances in radiotherapy for hepatocellular carcinoma[J].J Basic Clin Oncol,2015,(4):365-368.DOI:10.3969/j.issn.1673-5412.2015.04.037. [13] Li JY,Ou ZL,Yu SJ,et al. The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer[J].Breast Cancer Res Treat.2012,131(3):837-848.DOI:10.1007/s10549-011-1502-6. [14] Olkhanud PB,Baatar D,Bodogai M,et al. Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells[J].Cancer Res.2009,69(14):5996-6004.DOI:10.1158/0008-5472.CAN-08-4619. [15] Ou B,Zhao J,Guan S,et al. CCR4 promotes metastasis via ERK/NF-KappaB/MMP13 pathway and acts downstream of TNF-alpha in colorectal cancer[J].Oncotarget.2016,7(30):47637-47649.DOI:10.18632/oncotarget.18562.
2019, Vol. 28 
