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目的评估锌原卟啉(ZnPP)Ⅸ对肝癌耐药细胞株化疗药物敏感性及其表达血红素加氧酶-1(hemeoxygenase,HO-1)和谷胱甘肽-S-转移酶-π(glutathione-S-transferase-π,GST-π)的影响,探讨ZnPPⅨ作为化疗耐药逆转剂的可能性及相关作用机理。方法①ZnPPⅨ作用于肝癌耐药细胞株Bel/Fu后,应用MTT法检测阿霉素、丝裂霉素及5-氟尿嘧啶的半数抑制浓度(IC50)。②不同浓度ZnPPⅨ作用于Bel/Fu细胞后,应用RT-PCR法检测细胞HO-1及GST-πmRNA的表达量。结果 ZnPPⅨ作用于Bel/Fu细胞24 h后,各化疗药物的IC50均明显降低(P<0.05);HO-1 mRNA及GST-πmRNA的表达量显著降低(P<0.01),且均呈剂量依赖趋势(P<0.01)。结论 ZnPPⅨ通过抑制HO-1和GST-π的表达,使肝癌耐药细胞株的化疗敏感性增高。ZnPPⅨ可作为一种潜在的化疗耐药逆转剂。
Objective To evaluate the sensitivity of chemotherapeutic drugs induced by zinc protoporphyrin (Ⅵ) and its expression of hemeoxygenase (HO-1) and glutathione-S-transferase-π glutathione-S-transferase-π, GST-π) to explore the possibility and related mechanism of ZnPPⅨ as a chemoresistant reversal agent. Methods ①ZnPPⅨ was used to determine the half maximal inhibitory concentration (IC50) of doxorubicin, mitomycin and 5-fluorouracil using MTT assay after the cells were treated with Bel / Fu. ② After different concentrations of ZnPPⅨ on Bel / Fu cells, the expression of HO-1 and GST-πmRNA was detected by RT-PCR. Results The IC50 of all chemotherapeutic agents decreased significantly (P <0.05) after treated with ZnPPⅨ for 24 h. The mRNA and protein expressions of HO-1 and GST-π were significantly decreased (P <0.01) Trend (P <0.01). Conclusion ZnPPⅨ can inhibit the expression of HO-1 and GST-π in chemosensitivity of drug-resistant hepatocellular carcinoma cell lines. ZnPPⅨ can be used as a potential drug resistance reversal agent.