肺癌药敏与耐药基因MRP1、P-gp、GST-π和TopoⅡ表达的相关性研究

目的 研究多药耐药相关蛋白1 （MRP1）、P-糖蛋白（P-gp）、谷胱甘肽S转移酶-π（GST-π）、拓扑异构酶Ⅱ（TopoⅡ）基因表达和肺癌药物敏感试验相关性.方法 药物敏感试验采用MTT比色法,MRP1、P-gp、GST-π及TopoⅡ采用免疫组化检测.结果 MRP1、P-gp、GST-c及TopoⅡ在肺癌中总的阳性率分别为72.5％、67.5％、57.5％、50.0％.在鳞癌和腺癌中,这四种因子其表达无显著性差异（P＞0.05）,但P-gp、GST-π在鳞癌或腺癌中与在小细胞肺癌中表达有明显差异（P＜0.05）.P-gp和GST-π表达与顺铂、吉西他滨、长春瑞滨、紫杉醇耐药性呈正相关（P＜0.05）,与异环磷酰胺的耐药性无相关性（P ＞0.05）;MRP1的表达与顺铂、吉西他滨、长春瑞滨的耐药性均呈正相关（P＜0.05）,其表达与紫杉醇、异环磷酰胺的耐药性无相关性（P＞0.05）;TopoⅡ的表达与顺铂、吉西他滨、紫杉醇、异环磷酰胺的耐药性均呈正相关（P＜0.05）,其表达与长春瑞滨的耐药性无相关性（P＞0.05）.结论 MRP1、P-gp和GST-π的高表达及TopoⅡ的低表达共同介导参与了肺癌耐药的机制,且与检测的化疗药物耐药性有不同程度的相关性.

Relationship between drug sensitivity and expression of drug resistance genes in lung cancer

Objective To study the relationship between the expression of drug resistance genes （MRP1,P-gp,GST-π,and Topo Ⅱ） and the results of drug sensitivity test.Methods The drug sensitivity was measured by MTT colorimetric method.The drug resistance genes MRP1,P-gp,GST-π,and Topo Ⅱ were detected by immunohistochemistry.Results The expression percentages of MRP1,P-gp,GST-π,and Topo Ⅱ genes in lung cancer were 72.5 ％,67.5 ％,57.5 ％,50.0 ％.There was no significant difference in the expression of MRP1,P-gp,GST-π,and Topo Ⅱ between human adencarcinoma and sequamous cell carcinoma （P ＞0.05）,but there was significant difference in the expression of P-gp and GST-π between human adencarcinoma or sequamous carcinoma cell and small cell lung cancer （P ＜0.05）.There was positive correlation between the expression of P-gp and GST-π and the degrees of chemoresistance to cisplatin,gemcitabine,vinorelbine and paclitaxel （P ＜ 0.05）,but there was no correlation with iphspamide drug tolerance （P ＞0.05）.There was positive correlation between the expression of MRP1 and the degrees of chemoresistance to cisplatin,gemcitabine,and vinorelbine （P ＜0.05）,but there was no correlation with drug tolerance of paclitaxel and iphspamide （P ＞ 0.05）.Conclusions The high expression of MRP1,P-gp,GST-π and the low expression of Topo Ⅱ commonly mediate and partipate in the drug resistance mechanism of lung cancer,and have correlation with the chemotherapy drug resistance.