Guo Qing, Gao Bu-Lang, Zhang Xue-Jing, Liu Guo-Chao, Xu Feng, Fan Qiong-Ying, Zhang Shao-Jing, Yang Bo, Wu Xiao-Hua
Department of Obstetrics and Gynecology, Shijiazhuang First Hospital, Hebei Medical University, Shijiazhuang, China.
Oncol Res. 2014;22(5-6):247-58. doi: 10.3727/096504015X14343704124430.
The CXCL12-CXCR4 chemokine axis may play a very important role in ovarian cancer cells proliferation, migration, invasion, and peritoneal metastasis in vitro and in vivo. In this study, transfected SKOV3-CXCR4, transfected vector SKOV3-negative, nontransfected SKOV3 ovarian cancer cells, and human peritoneal mesothelial cells (HPMCs) were cultivated in vitro, and the proliferation, migration, and invasion of these ovarian cancer cells were investigated with or without the influence of the CXCL12-CXCR4 axis. Nude mice models of ovarian cancer were created by injection of ovarian cancer cells into the peritoneal cavity for investigation of ovarian cancer cells metastasis. Our results demonstrated that in the SKOV3-CXCR4 group, the cell number of proliferation, migration, or penetration through the Matrigel membrane treated with CXCL12 was significantly (p < 0.05) greater than those treated with CXCR4 antibody or CXCR4 antagonist AMD 3100 in a concentration-dependent manner. In the SKOV3-negative and the nontransfected SKOV3 groups, no significant (p > 0.05) differences existed in the cell number of proliferation, migration, or penetration. Coculture of HPMCs and SKOV3-CXCR4 had significantly (p < 0.05) higher migration and invasion rates than the SKOV3-CXCR4-only group. In nude mice seeded with ovarian cancer cells, the tumor weight in the nude mice injected with SKOV3-CXCR4 cells was significantly (p < 0.05) greater than in the group injected with the SKOV3-negative or nontransfected SKOV3 cells. Taken together, our results show that the CXCL12-CXCR4 chemokine axis can significantly promote the proliferation, migration, invasion, and peritoneal metastasis of ovarian cancer cells, and interference with this axis may serve as a new therapeutic target in treating ovarian cancers.
CXCL12 - CXCR4趋化因子轴可能在体外和体内的卵巢癌细胞增殖、迁移、侵袭及腹膜转移过程中发挥非常重要的作用。在本研究中，体外培养转染了SKOV3 - CXCR4的细胞、转染空载体的SKOV3阴性细胞、未转染的SKOV3卵巢癌细胞以及人腹膜间皮细胞（HPMCs），并在有或无CXCL12 - CXCR4轴影响的情况下，研究这些卵巢癌细胞的增殖、迁移和侵袭能力。通过向裸鼠腹腔注射卵巢癌细胞建立卵巢癌裸鼠模型，以研究卵巢癌细胞转移情况。我们的结果表明，在SKOV3 - CXCR4组中，经CXCL12处理的增殖、迁移或穿透基质胶膜的细胞数量，以浓度依赖方式显著（p < 0.05）多于经CXCR4抗体或CXCR4拮抗剂AMD 3100处理的细胞数量。在SKOV3阴性组和未转染的SKOV3组中，增殖、迁移或穿透的细胞数量无显著（p > 0.05）差异。HPMCs与SKOV3 - CXCR4共培养组的迁移和侵袭率显著（p < 0.05）高于仅SKOV3 - CXCR4组。在接种卵巢癌细胞的裸鼠中，注射SKOV3 - CXCR4细胞的裸鼠肿瘤重量显著（p < 0.05）大于注射SKOV3阴性细胞或未转染的SKOV3细胞的组。综上所述，我们的结果表明，CXCL12 - CXCR4趋化因子轴可显著促进卵巢癌细胞的增殖、迁移、侵袭及腹膜转移，干扰该轴可能成为治疗卵巢癌的新靶点。
