子宫颈癌组织三磷酸腺苷肿瘤体外药物敏感试验及其与耐药蛋白表达的关系

目的探讨三磷酸腺苷肿瘤体外药物敏感试验（ATP-TCA）用于检测宫颈癌组织对化疗药物敏感性的可行性,分析耐药蛋白P糖蛋白（P—gp）、谷胱甘肽巯基转移酶π（GST-π）、胸苷酸合成酶（as）的表达与ATP-TCA结果的关系。方法采用ATP—TCA对35例宫颈癌患者的新鲜癌组织进行体外药物敏感试验,分别检测宫颈癌组织对紫杉醇、顺铂、博来霉素、吉西他滨、5氟尿嘧啶、依立替康6种化疗药物的敏感性;采用免疫组化法检测35例宫颈癌患者癌组织中p-gp、GST-π、TS蛋白的表达;分析ATP-TCA结果与P-gp、GST-π、鸭蛋白表达的关系。结果（1）35份宫颈癌标本中,32份标本成功进行了ATP-TCA检测,ATP—TCA的可评价率为91％。宫颈癌组织对药物的敏感率分别为紫杉醇88％（28／32）、5氟尿嘧啶72％（23／32）、吉西他滨62％（20／32）、顺铂19％（6／32）、博来霉素16％（5／32）、依立替康12％（4／32）。（2）GST-π、鸭蛋白的高表达率分别为66％（21／32）、44％（14／32）]与宫颈癌组织体外对顺铂、5氟尿嘧啶的耐药有相关性（P=0．011、P=0．022）,P-gp蛋白的阳性表达率41％（13／32）]与宫颈癌组织体外对紫杉醇、5氟尿嘧啶、吉西他滨、顺铂、依立替康、博来霉素的耐药无相关性（P＞0．05）。结论ATP-TCA可用于宫颈癌患者个体化化疗的药物筛选。GST-π、鸭蛋白可能是预测宫颈癌患者对顺铂、5氟尿嘧啶耐药的标志物。

Relationship between the expression of P-glycoprotein, glutathione S-transferase-pi and thymidylate synthase proteins and adenosine triphosphate tumor chemosensitivity assay in cervical cancer

OBJECTIVE: To explore the feasibility of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in human cervical cancer chemosensitivity testing and to analyze the relationship between the three drug resistance-associated proteins: P-glycoprotein (P-gp); glutathione S-transferase-pi (GST-pi); thymidylate synthase (TS) and ATP-TCA. METHODS: ATP-TCA was used to detect the sensitivity of 35 specimens of fresh cervical cancer to six cytotoxic drugs as follows: paclitaxel (TAX), cisplatin (DDP), bleomycin (BLM), gemcitabine (GEM), 5-fluorouracil (5-FU), irinotecan (CPT-11). Consecutive sections from 35 cases of cervical cancer were assessed immunohistochemically for expression of P-gp, GST-pi and TS proteins. RESULTS: (1) Thirty-two of 35 assays were completed successfully, with an evaluability rate of ATP-TCA at 91% (32/35). There was a marked heterogeneity of chemosensitivity in cervical cancer. The ex vivo sensitive rate of TAX was 88% (28/32), of 5-FU 72% (23/32), of GEM 62% (20/32), of DDP 19% (6/32), of BLM 16% (5/32), and of CPT-11 12% (4/32). (2) The expression of GST-pi and TS protein in cervical cancer was 66% (21/32) and 44% (14/32), which was associated with the resistance to DDP and 5-FU ex vivo (P=0.011, P=0.022), respectively; but the expression of P-gp protein was not associated with any resistance to TAX, 5-FU, GEM, DDP, BLM or CPT-11 ex vivo (P>0.05). CONCLUSIONS: ATP-TCA could be used to individualize chemotherapy by selecting agents for particular patients of cervical cancer. The expression of GST-pi and TS protein might be useful biomarkers to predict the resistance to DDP and 5-FU in patients with cervical cancer.