乳癌术后方通过SDF-1/CXCR4生物轴对MDA-MB-453乳腺癌细胞增殖和转移的影响  

Effect of Ru ′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis

作　　者：李艳敏 吴雪卿[1] 万华[1] 邵士珺[1] 丁思奇 LI Yan-min;WU Xue-qing;WAN Hua;SHAO Shi-jun;DING Si-qi(Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)

机构地区：[1]上海中医药大学附属曙光医院,上海200021

出　　处：《中国实验方剂学杂志》2020年第23期106-112,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：上海市科学技术委员会科研计划项目(18ZR1440300)。

摘　　要：目的:以基质细胞衍生因子-1(Stromal cell-derived factor-1,SDF-1)/趋化因子受体4(Chemokine receptor,CXCR4)生物轴为基础,探讨乳癌术后含药血清对乳腺癌细胞MDA-MB-453增殖和侵袭能力的影响。方法:建立SDF-1诱导的CXCR4高表达MDA-MB-453细胞模型,制备乳癌术后方含药血清及空白大鼠血清。实验分空白组,空白大鼠血清组,SDF-1+空白大鼠血清组,SDF-1+乳癌术后方组,AMD3100+SDF-1+空白大鼠血清组和AMD3100+SDF-1+乳癌术后方组。干预48 h,采用cell counting kit-8(CCK-8)法检测细胞增殖情况,transwell小室实验检测细胞侵袭能力,分别用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测细胞CXCR4,基质金属蛋白酶(matrix metalloproteinase,MMP)-2,MMP-9 mRNA及蛋白表达情况。结果:与空白血清组比较,SDF-1为100μg·L-1时,MDA-MB-453细胞增殖明显,CXCR4 mRNA表达明显增加(P<0.05);与SDF-1+空白大鼠血清组比较,乳癌术后方能抑制SDF-1诱导的MDA-MB-453细胞增殖、侵袭行为,下调CXCR4,MMP-2,MMP-9 mRNA和蛋白表达水平(P<0.05);经AMD3100预处理24 h,乳癌术后方对MDA-MB-453细胞增殖的抑制作用明显增强(P<0.05);同时,乳癌术后方下调CXCR4,MMP-2,MMP-9 mRNA和蛋白表达的作用明显增加(P<0.05)。结论:乳癌术后方可通过调控SDF-1/CXCR4生物轴,降低MDA-MB-453细胞MMP-2,MMP-9表达,减少细胞外基质(extracellular matrix,ECM)降解,进而抑制乳腺癌细胞转移的发生;与CXCR4抑制剂AMD3100具有协同效应。Objective: To investigate the effect of Ru′ai Shuhou prescription(RSR)drug-containing serum on the proliferation and invasion ability of breast cancer cells MDA-MB-453 based on the biological axis of stromal cell-derived factor-1(SDF-1)/chemokine receptor 4(CXCR4). Method:A model of MDA-MB-453 cells with SDF-1-induced high expression of CXCR4 was established,and the rat drug-serum containing RSR and blank rat serum were prepared respectively. The cells were divided into fetal bovine serum control group(Blank),blank rat serum group,SDF-1+blank rat serum group,SDF-1+RSR group,AMD3100+ SDF-1+blank rat serum group,and AMD3100+SDF-1+RSR group. After intervention for 48 h,cell proliferation was detected by cell counting kit-8(CCK-8)assay,cell invasion ability was detected by transwell assay,and mRNA and protein expressions of CXCR4,matrix metalloproteinase-2(MMP-2)and MMP-9 were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot,respectively. Result:As compared with the blank serum group,the proliferation of MDA-MB-453 cells was promoted and expression of CXCR4 mRNA was increased significantly when SDF-1 was 100 μg·L-1(P<0.05). As compared with SDF-1+blank rat serum group,RSR inhibited the proliferation and invasion of MDA-MB-453 cells induced by SDF-1,and at the same time,down-regulated the mRNA and protein expressions of CXCR4,MMP-2 and MMP-9(P<0.05). After pre-treatment with AMD3100 for 24 h,the inhibitory effect of RSR to cell proliferation was significantly increased(P<0.05),and meanwhile,the decreases in mRNA and protein expression of CXCR4,MMP-2 and MMP-9 were more obvious, with statistically significant differences(P<0.05). Conclusion:Through SDF-1/CXCR4 biological axis,RSR could down-regulate the expression of MMP-2 and MMP-9,reduce the degradation of extracellular matrix(ECM),and then inhibit the metastasis of MDA-MB-453 cells. In addition,it has a synergistic effect with CXCR4 inhibitor AMD3100.

关 键 词：乳腺癌 乳癌术后方 基质细胞衍生因子-1(SDF-1)/趋化因子受体4(CXCR4)生物轴 基质金属蛋白酶 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]