Hepatocyte growth factor/c-Met signaling pathway decreases doxorubicin sensitivity in hepatocellular carcinoma in vitro
10.3760/cma.j.issn.1006-9801.2017.05.001
- VernacularTitle: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
- Author:
Dhruba KADEL
;
Yu ZHANG
;
Haoran SUN
;
Qiongzhu DONG
;
Lunxiu QIN
- Keywords:
Carcinoma,hepatocellular;
Hepatocyte growth factor;
Doxorubicin;
Signal transduction
- From:
Cancer Research and Clinic
2017;29(5):289-293,299
- CountryChina
- Language:Chinese
-
Abstract:
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.
