Topotecan inhibits cancer cell migration by down-regulation of chemokine CC motif receptor 7 and matrix metalloproteinases  

作　　者：Sen-sen LIN Li SUN Yan-kai ZHANG Ren-ping ZHAO Wen-lu LIANG Sheng-tao YUAN Lu-yong ZHANG 

机构地区：[1]National New Drug Screening Lab, China Pharmaceutical University, Nanjing 210009 [2]jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210038, China

出　　处：《Acta Pharmacologica Sinica》2009年第5期628-636,共9页中国药理学报（英文版）

基　　金：Acknowledgements This project was financially supported by the National High Technology Research and Development Program of China （863 Program, No 2004AA2Z3785） and by a grant from the Natural Science Foundation of Jiangsu province （No BK2006150）.

摘　　要：Aim： The aim of this study was to investigate the effect of topotecan （TPT） on cancer cell migration. Methods： Growth inhibition of TPT was analyzed by MTT assay, and cancer cell migration was measured by transwell double chamber assay. To verify the effect of TPT on the chemokine receptors CXCR4 and CCR7, quantitative PCR, semiquantitative PCR and Western blot analysis were performed. The secretion of MMP-2 and MMP-9 was detected by enzymelinked immunosorbent assay （ELISA） and gelatin zymography. To evaluate possible contributions of CCR7 to MMP secre- tion, the overexpression vectors pcDNA3.1^＋-CCR7 and CCR7 siRNA were transiently transfected into MDA-MB-435 cells. Results： TPT inhibited cancer cell migration in a dose-dependent manner. Additionally, TPT significantly decreased the expression of CCR7 in both MDA-MB-435 and MDA-MB-231 cells and moderately reduced the expression of CXCR4 in MDA-MB-435 cells. The secretion of MMPs （MMP-2, MMP-9） was also inhibited by TPT. Overexpression of CCR7 increased the secretion of MMP-2/9 and cancer cell migration, whereas knockdown of CCR7 reduced active MMP-2/9 production and migration of MDA-MB-435 cells. Conclusion： TPT inhibited cancer cell migration by down-regulation of CCR7 and MMPs （MMP-2 and MMP-9）.Aim： The aim of this study was to investigate the effect of topotecan （TPT） on cancer cell migration. Methods： Growth inhibition of TPT was analyzed by MTT assay, and cancer cell migration was measured by transwell double chamber assay. To verify the effect of TPT on the chemokine receptors CXCR4 and CCR7, quantitative PCR, semiquantitative PCR and Western blot analysis were performed. The secretion of MMP-2 and MMP-9 was detected by enzymelinked immunosorbent assay （ELISA） and gelatin zymography. To evaluate possible contributions of CCR7 to MMP secre- tion, the overexpression vectors pcDNA3.1^＋-CCR7 and CCR7 siRNA were transiently transfected into MDA-MB-435 cells. Results： TPT inhibited cancer cell migration in a dose-dependent manner. Additionally, TPT significantly decreased the expression of CCR7 in both MDA-MB-435 and MDA-MB-231 cells and moderately reduced the expression of CXCR4 in MDA-MB-435 cells. The secretion of MMPs （MMP-2, MMP-9） was also inhibited by TPT. Overexpression of CCR7 increased the secretion of MMP-2/9 and cancer cell migration, whereas knockdown of CCR7 reduced active MMP-2/9 production and migration of MDA-MB-435 cells. Conclusion： TPT inhibited cancer cell migration by down-regulation of CCR7 and MMPs （MMP-2 and MMP-9）.

关 键 词：TOPOTECAN MDA-MB-435 MDA-MB-231 cancer metastasis CXCR4 CCR7 MMP-2 MMP-9 

分 类 号：R587.2[医药卫生—内分泌] R512.91[医药卫生—内科学]