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Overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis in hepatocellular carcinoma
Jun Ding1,2,3,#, Kangdi Xu1,2,3,#, Jie Zhang1,6, Bingyi Lin1,5, Yubo Wang1,2,3, Shengyong Yin2,3,4, Haiyang Xie2,3,4, Lin Zhou3,4,5, Shusen Zheng1,2,3,*
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital School of Medicine, Zhejiang University,
2Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health,
3Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences,
4Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou. China,
5Collaborative Innovation Center for Diagnosis treatment of infectious diseases, Hangzhou, Zhejiang 310003, P.R. China,
6Department of Hepatobiliary Surgical, First Hospital of Jiaxing, Jiaxing, Zhejiang 314000, P.R.China
Abstract
C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of ELR+ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.
Abstract, Accepted Manuscript(in press) [Submitted on July 5, 2018, Accepted on October 2, 2018]
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