进展期肝细胞癌分子靶向药物治疗疗效预测动物模型的建立

Establishment of Animal Models for Prediction of Therapeutic Efficacy of Molecularly Targeted Agents on Advanced Hepatocellular Carcinoma

目的建立肝细胞癌(hepatocellular carcinoma,HCC)分子靶向治疗药物药效学检验与预测模型。方法本次实验选择了MHCC97-H细胞(高侵袭性的HCC细胞系)建立了裸鼠皮下肿瘤模型、肝脏原位接种HCC组织模型、肝门静脉注射HCC细胞模型;选取分子靶向药物索拉非尼(sorafenib)、阿帕替尼(apatinib)以及安罗替尼(anlotinib)为模式药物;裸鼠灌胃给予2 mg·kg^-1的索拉非尼、阿帕替尼以及安罗替尼进行治疗后,确定这些分子靶向药物对不同肿瘤模型的抗肿瘤作用,计算药物抑制肿瘤细胞生长的抑制率。结果索拉非尼、阿帕替尼以及安罗替尼均能够显著抑制不同模型中MHCC97-H细胞的生长,阿帕替尼以及安罗替尼的作用较优于索拉非尼。结论本实验成功建立了分子靶向药物治疗进展期肝细胞癌疗效预测动物模型。

OBJECTIVE To establish a pharmacodynamics testing and predicting model for molecular targeted therapy of advanced hepatocellular carcinoma(HCC).METHODS MHCC97-H(a highly aggressive HCC cell line)cells were cultured to establish:①a subcutaneous tumor model in nude mice,②an in situ HCC tissue seeding model,③a hepatic portal vein injection of HCC cell model.Nude mice were intragastric admistrated with 2 mg·kg^-1 of sorafenib,apatinib or anlotinib per two days.The antitumor effect of sorafenib,apatinib and anlotinib was examined.RESULTS Sorafenib,apatinib and anlotinib could significantly inhibit the growth of HCC cells in different models,and the effect of apatinib and anlotinib was better than that of sorafenib.CONCLUSION By establishing tumor models of HCC in nude mice,this work provides a strategy to examine the potential antitumor activation of agents for advanced HCC.