Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide.
Aim: To investigate the mechanisms of paclitaxel resistance in hepatocellular carcinoma cells and find promising molecular target for HCC therapy.
Materials and methods: To investigate the effects of FHL1 on chemo resistance in HCC cells, we generated FHL1 knock-down stable cell lines with HepG2 and SMMC7721 cells. Cell viability assay, colony formation and xenograft experiments assay were performed to detect effect of FHL1 on Paclitaxel or Oxaliplatin resistance in vitro and in vivo. Caspase activity assay was performed to explore the activation of caspase-3 and caspase-9 in paclitaxel treated FHL1-knockdown HepG2 cells.
Result: In the present study we have investigated that four-and-a-half LIM protein 1 (FHL1), which plays an important role in the development of cancer, is associated with both the chemo resistance of hepatocellular carcinomas cells in vitro and in vivo. Knockdown of FHL1 significantly enhanced the sensitivity of paclitaxel, but had no effects on sensitivity of oxaliplatin. Moreover, knockdown of FHL1 promoted the activation of caspase-3 and caspase-9, which were induced by paclitaxel. Interestingly, FHL1 negatively regulates the chemo resistance of HCC in xenografted nude mice.
Conclusion: FHL1 promote paclitaxel resistance in hepatocellular carcinomas cells through regulating apoptosis induced by paclitaxel, suggesting that FHL1 may be a promising molecular target for HCC therapy.
Keywords: Caspase-3; drug resistance; four-and-a-half LIM protein 1; paclitaxel.