姜黄素纳米粒(NanoCurc)联合索拉非尼对肝细胞癌(HCC)的协同抑制作用

被引:2
作者
胡博
孙超
孙鼎
孙云帆
徐泱
机构
[1] 复旦大学附属中山医院肝癌研究所
关键词
肝细胞癌(HCC); 姜黄素纳米粒(NC); 索拉非尼; 基质金属蛋白酶-9(MMP-9);
D O I
暂无
中图分类号
R735.7 [肝肿瘤];
学科分类号
摘要
目的探讨姜黄素纳米粒(NanoCurcTM,NC)单药或联合索拉非尼对人肝细胞癌(hepatocellular carcinoma,HCC)的作用。方法采用体外细胞增殖检测试剂盒(CCK-8)、体外划痕试验和Transwell侵袭试验法检测NC和/或索拉非尼对肝癌细胞株MHCCLM3增殖、迁移、侵袭能力的影响;应用流式细胞术分析其对细胞凋亡的作用。建立裸鼠MHCCLM3原位移植模型并观察NC和/或索拉非尼对肿瘤大小和肺转移率的影响。应用RTPCR、ELISA、Western blot法检测基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、细胞外信号调节激酶1/2(ERK1/2)mRNA或相应蛋白表达变化;并测定ERK1/2的磷酸化变化。结果 NC与索拉非尼联合应用可显著抑制HCC体外增殖和侵袭能力(P<0.01),抑制体内肿瘤生长和肺转移(P<0.01)。单独应用NC和索拉非尼时肺转移率分别为50.0%和66.7%,两者联合用药时则显著降低至16.7%。两药联合应用可协同抑制ERK磷酸化,从而下调MMP-9的表达。结论 NC联合索拉非尼可通过协同诱导细胞凋亡、抑制MMP-9的表达而抑制肝癌生长和转移。
引用
收藏
页码:143 / 148
页数:6
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