| Background&Purpose:Hepatocellular carcinoma(HCC) is the fifth most common type of cancer and is the third leading cause of cancer-related deaths worldwide. Advanced HCC patients often accompany with Portal vein tumor thrombosis(PVTT), which will leads to a poor prognosis. Systemic chemotherapy is one option for the treatment of advanced and metastasis HCC patients, however their efficacy is limited by the development of resistance, so enhance the efficacy of treating chemotherapy resistant HCC patients become urgent. In this article,we study the effect of oxaliplatin combined ATRA on HCC associated resistant cell lines and its possible mechanism, aimed to direct clinical practice.Methods:Hep3b and CSQT-2 resistant cell lines were established about one years by different concentration of oxaliplatin.We find a novel chemotherapeutic methods to treat resistant-HCC, by characterized the function of combinatorial treatment with oxaliplatin and ATRA in vitro and in vivo.Results:Oxaliplatin combined ATRA effectively inhibit the proliferation of Hep3 b and PVTT derived CSQT-2 resistant cell lines compared with control group in vitro and in vivo.In addition,the combinatorial group also arrest the two resistant cell lines cell cycle at G2/M phase by up-regulating cylinB protein. Moreover, the combinatorial treatment of oxaliplatin and ATRA show strongly inhibition on either HCC cell migration compared to the treatment with either drug alone.Conclusions:Our results showed that ATRA combined oxaliplatin arrest Hep3 b and CSQT resistant cell lines cell cycle at G2/M phrase, and then inhibit the proliferation of resistant HCC celllines.Potential applications and novelty:Our results firstly demonstrated that ATRA combined oxaliplatin can effectively inhibit resistant HCC cell lines and its possible mechanism.This results will provide basic theory for chosing the best chemotherapeutic approach. |
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