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肝细胞生长因子/c-Met信号通路降低体外肝细胞癌细胞对多柔比星的敏感性
  • ISSN号:1006-9801
  • 期刊名称:《肿瘤研究与临床》
  • 时间:0
  • 分类:R692[医药卫生—泌尿科学;医药卫生—临床医学;医药卫生—外科学]
  • 作者机构:[1]复旦大学附属华山医院普外科,上海200040, [2]复旦大学肿瘤转移研究所,上海200040, [3]复旦大学生物医学研究院,上海200032
  • 相关基金:国家重大科学研究计划(S973计划)(2013CB910500);国家重点基础研究发展计划(973计划)(2014CB542101)
中文摘要:

目的 探讨肝细胞生长因子(HGF)/c-Met信号通路体外对多柔比星(DOX)作用肝细胞癌(HCC)细胞株的影响.方法 以不同生物学特性和遗传特征的HCC细胞株Huh7、HepG2、MHCC97-L和MHCC97-H作为研究对象.通过实时定量聚合酶链反应(RT-PCR)检测不同HCC细胞株中c-Met mRNA的表达,通过蛋白印迹法分析不同药物处理下这些细胞株中c-Met和磷酸化Met(p-Met)的表达水平.通过CCK-8实验分析不同细胞株对DOX的敏感性.组间统计学比较采用重复测量的方差分析和t检验.结果 相较于Huh7和HepG2细胞株,MHCC97-L和MHCC97-H细胞株高表达c-Met和p-Met mRNA,并且对DOX不敏感.HGF能够激活Huh7和HepG2细胞株的c-Met信号通路,并降低Huh7和HepG2细胞对DOX的敏感性[对Huh7细胞抑制率:(34.848±5.370)%比(66.409±5.792)%;对HepG2细胞抑制率:(34.351±3.305)%比(62.308±5.453)%;均P=0.002].而使用c-Met抑制剂则增强DOX对MHCC97-L和MHCC97-H细胞的抑制作用[对MHCC97-L细胞抑制率:(73.106±3.472)%比(13.636±4.097)%;对MHCC97-H细胞抑制率:(64.444±4.006)%比(6.296±2.796)%;均P〈0.001].结论 HGF/c-Met信号通路与体外DOX作用HCC细胞的效果密切相关.

英文摘要:

Objective To explore the effect of hepatocyte growth factor (HGF)/c-Met signaling in doxorubicin (DOX) treatment of hepatocellular carcinoma (HCC). Methods Different biologic and genetic characteristics human HCC cell lines, Huh7, HepG2, MHCC97-L and MHCC97H were used in this experiment. Variation in c-Met mRNA expression level among different HCC cell lines was analyzed by RT-PCR. Western blot analysis was performed to detect c-Met and p-Met expression levels in these cell lines. CCK-8 experiment was carried to analyze the DOX sensitivity in various cell lines. t test and repeated measure analysis of variance were used for statistical analysis. Results Both c-Met and p-Met were overexpressed in MHCC97-L and MHCC97-H cell lines and these cell lines were resistant to DOX compared to Huh7 and HepG2. However, treatment of HGF in Huh7 and HepG2 cells activated c-Met signaling pathway and decreased the sensitivity of these two cell lines to DOX [inhibition rate: Huh7 (34.848 ±5.370) vs. (66.409±5.792)%, HepG2 (34.351±3.305) %vs. (62.308±5.453) %, both P=0.002]. Whereas administration of c-Met inhibitor in MHCC97-L and MHCC97-H cell lines significantly increased the sensitivity to DOX [inhibition rate: MHCC97-L (73.106 ±3.472) % vs. (13.636 ±4.097) %; MHCC97-H (64.444 ±4.006) % vs. (6.296 ±2.796) %, both P〈 0.001]. Conclusion HGF/c-Met signaling pathway is related the treatment efficacy of DOX in HCC.

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期刊信息
  • 《肿瘤研究与临床》
  • 中国科技核心期刊
  • 主管单位:卫生部
  • 主办单位:中华医学会 山西省肿瘤研究所 山西省肿瘤医院
  • 主编:
  • 地址:太原市职工新街3号
  • 邮编:030013
  • 邮箱:zlyjylc@sina.com
  • 电话:0351-4650389 4650386
  • 国际标准刊号:ISSN:1006-9801
  • 国内统一刊号:ISSN:11-5355/R
  • 邮发代号:22-137
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国剑桥科学文摘,中国中国科技核心期刊
  • 被引量:9654