论文部分内容阅读
目的探讨肺癌耐药机制及明确耐药基因与化疗药物耐药性的相关性研究。方法应用MTT法对顺铂(Cisplatin),吉西他滨(Gemcitabine),长春瑞滨(Vinorelbine),紫杉醇(Paclitaxel),异环磷酰胺(Iphospamide)5种化疗药物针对肺癌细胞悬液进行药敏检测;应用免疫组化进行MRP1(多药耐药相关蛋白1)及TopoⅡ(拓扑异构酶Ⅱ)表达的检测,并将其表达情况与对应的化疗耐药性进行相关分析。结果①MRP1、TopoⅡ在肺癌中总的阳性表达率分别为:72.5%、50.0%。鳞癌和腺癌MRP1、TopoⅡ相比的表达差异无统计学意义(P>0.05),但鳞癌或腺癌和小细胞肺癌在MRP1、TopoⅡ表达相比差异有统计学意义(P<0.05);②MRP1的表达与顺铂、吉西他滨、长春瑞滨的耐药性均呈显著的正相关(P<0.05),其表达与紫杉醇、异环磷酰胺的耐药性差异无统计学意义(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显著的正相关(P<0.05),其表达与长春瑞滨的耐药性差异无统计学意义(P>0.05)。结论①MRP1较高表达及TopoⅡ的较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有不同程度的相关性。②应用肿瘤细胞体外培养、进行体外药敏检测,并明确耐药基因的表达情况,对于识别可能的耐药个体,选择合理有效的化疗药物,可能将会最大限度地避免无效化疗和提高化疗疗效。
Objective To investigate the mechanism of drug resistance in lung cancer and the relationship between drug resistance and drug resistance. Methods MTT assay was used to detect the drug sensitivity of 5 chemotherapeutic agents including Cisplatin, Gemcitabine, Vinorelbine, Paclitaxel and Iphospamide against lung cancer cell suspension. The expression of MRP1 (multidrug resistance-associated protein 1) and TopoⅡ (topoisomerase Ⅱ) were detected by immunohistochemistry, and the correlation between the expression of MRP1 and corresponding chemoresistance was analyzed. Results ① The positive rates of MRP1 and Topo Ⅱ in lung cancer were 72.5% and 50.0% respectively. There was no significant difference between squamous cell carcinoma and adenocarcinoma MRP1 and TopoⅡ (P> 0.05), but there was significant difference between MRP1 and Topo Ⅱ in squamous cell carcinoma or adenocarcinoma and small cell lung cancer (P <0.05) ; ② The expression of MRP1 was positively correlated with the drug resistance of cisplatin, gemcitabine and vinorelbine (P <0.05), and there was no significant difference in the drug resistance between paclitaxel and ifosfamide (P> 0.05). There was a significant positive correlation between the expression of TopoⅡ and the drug resistance of cisplatin, gemcitabine, paclitaxel and ifosfamide (P <0.05), and no significant difference was found between the expression of TopoⅡ and the drug resistance of vinorelbine P> 0.05). Conclusion ① The higher expression of MRP1 and the lower expression of TopoⅡ are involved in the mechanism of drug resistance in lung cancer, and have some correlation with the tested chemotherapeutics. ②Tumor cells cultured in vitro, drug susceptibility testing in vitro, and clear the expression of drug resistance genes for the identification of possible resistant individuals, select a reasonable and effective chemotherapy drugs, may be to maximize the effectiveness of chemotherapy to avoid ineffective and improve the efficacy of chemotherapy .