宫颈鳞状细胞癌ATP-TCA法体外药敏试验与耐药相关蛋白表达的关系

目的:探讨代表不同耐药机制的P糖蛋白(P-gp)、谷胱甘肽S-转移酶(GST-π)、DNA拓扑异构酶Ⅱ(TopoⅡ)、胸苷酸合成酶(TS)在原发宫颈鳞癌组织中的表达及其与临床病理参数的关系;分析三磷酸腺苷生物荧光法体外药敏试验(ATP-TCA)结果与耐药蛋白表达的关系。方法:收集32例宫颈鳞癌患者的新鲜癌组织制成单细胞悬液,采用ATP-TCA法成功检测上述细胞对11种化疗药物(共16种组合)的体外敏感性;采用EnVision二步法免疫组化检测32例宫颈鳞癌组织中P-gp、GST-π、TopoⅡ、TS蛋白的表达,并分析其与临床分期、肿瘤分化程度的关系。结果:耐药蛋白P-gp、GST-π、TopoⅡ、TS在宫颈鳞癌组织中的表达与临床分期、肿瘤分化程度无相关性;耐药蛋白P-gp表达与体外PTX+CBP耐药正相关(P=0.040);耐药蛋白TS表达与体外5-FU、5-FU+MMC、5-FU+DDP耐药正相关(P=0.015,0.012,0.006);TopoⅡ,GST-π蛋白表达与宫颈鳞癌体外耐药均无相关性。结论:体外药敏试验联合免疫组化检测,有可能用于宫颈鳞癌化疗前药敏预测。

Detection of chemosensitivity with ATP-TCA and the relationship between its results and the expression of drug resistance-associated proteins in cervical squamous cell carcinoma

Objective:To investigate the expression of drug resistance-associated proteins P-glycoprotein(P-gp),glutathione S-transferase-pi(GST-π),topoisomerase Ⅱ(TopoⅡ)and thymidylate synthase proteins(TS)in primary cervical squamous cell carcinoma and their clinical significance.To analyze the relationship between the ATP-TCA and the drug resistance-associated proteins.Methods:ATP-TCA was used to detect the sensitivity of 32 specimens of fresh cervical squamous cell carcinoma to 11 cytotoxic drugs(16 grapes).EnVision immunohistochemical method was used to detect the expression of P-gp,GST-π,TopoⅡand TS in 32 cases of cervical squamous cell carcinoma.Results:No significant association was found between the expression of P-gp,GST-π,TopoⅡ,TS protein and clinicopathologic feature such as clinical stage and cell differentiation;the expression of P-gp protein in cervical squamous cell carcinoma was associated wih the resistance to PTX+CBP ex vivo(P=0.040);the expression of TS protein in cervical squamous cell carcinoma was associated wih the resistance to 5-FU,5-FU+MMC and 5-FU+DDP ex vivo(P=0.015,0.012,0.006);the expression of TopoⅡand GST-π proteins was not associated with any resistance to ex vivo.Conclusions:chemosensitivity testing combined immunohistochemical detection may be used for chemotherapy sensitivity prediction of cervical squamous cell carcinoma.