胃癌组织中TPX2与肿瘤细胞铂类药物耐药的关系及意义

Relationship and significance of TPX2 in drug resistance of gastric cancer for platinum chemotherapy drugs

目的检测胃癌组织、癌旁正常组织的Xklp2靶蛋白(targeting protein for Xklp2,TPX2)和耐药相关蛋白的表达,同时检测这些组织对顺铂(cisplatin,CDDP)、奥沙利铂(oxaliplatin,L-OHP)的敏感性,探讨TPX2在胃癌铂类药物耐药中的作用。方法收集85例手术切除的胃癌组织、30例癌旁正常组织的新鲜及石蜡标本;胃癌组织按术前接受新辅助治疗情况分为术前化疗组25例、术前未化疗组60例,癌旁正常组织30例。检测CDDP和L-OHP对3组细胞的抑制率以及CDDP和L-OHP对TPX2阳性者和TPX2阴性者细胞的抑制率,石蜡组织进行免疫组织化学染色,检测TPX2及P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶π(glutathione S transferase-π,GST-π)、B淋巴细胞/白血病2(B lymphatic leukaemia 2,Bcl-2)等耐药相关蛋白的表达。MTT法检测新鲜组织的细胞对CDDP、L-OHP的敏感性。结果 CDDP和L-OHP对3组细胞的抑制率比较,CDDP和L-OHP对术前化疗组和术前未化疗组的抑制率均低于癌旁正常组织,CDDP和L-OHP对术前化疗组细胞的抑制率又低于术前未化疗组(P<0.05);CDDP和L-OHP对胃癌患者中TPX2阳性者细胞的抑制率低于TPX2阴性者(P<0.05);术前化疗组和术前未化疗组TPX2、P-gp、GST-π和Bcl-2蛋白表达均高于癌旁正常组织,术前化疗组TPX2蛋白的表达又高于术前未化疗组(P<0.05)。结论 TPX2可通过调节耐药相关蛋白参与了胃癌耐药形成的过程,该蛋白的表达在化疗过程中发生了变化。

Objective To test expressions of targeting protein for Xklp2(TPX2) in gastric cancer and adjacent normal tissues, also chemosensitivity to cisplatin(CDDP), oxaliplatin(L-OHP), to investigate drug resistant related proteins, and to explore the effect of TPX2 in drug resistance of platinum-based drugs in gastric cancer. Methods The fresh tissues and paraffin specimens of 85 cases gastric cancer, 30 cases of adjacent normal tissues were collected. Tissues of cases gastric cancer were divided into chemotherapy group, non-chemotherapy group, and adjacent normal tissues group. Expressions of TPX2 and P-glycoprotein(P-gp), glutathione S transferase-π(GST-π), B lymphatic leukaemia 2(Bcl-2) were tested with immunohistochemistry. MTT assay was applied to detect chemosensitivity of fresh tissues in each group to CDDP, L-OHP. Results MTT assay showed that inhibition rates of CDDP, L-OHP to chemotherapy group, non-chemotherapy group were lower than adjacent normal tissues group, and inhibition rates of CDDP, L-OHP to chemotherapy group were lower than non-chemotherapy group(P<0.05). Inhibition rates of CDDP, L-OHP to positive TPX2 group were lower than negative TPX2 group(P<0.05). Positive rates of TPX2, P-gp, GST-π, Bcl-2 proteins in chemotherapy group, non-chemotherapy group were higher than that of adjacent normal tissues, and positive rates of these proteins in chemotherapy group were higher than that in non-chemotherapy group(P<0.05). Conclusion The TPX2 protein might be involved in drug resistance of gastric cancer by regulating some drug resistance related proteins, and expression of TPX2 changed in the process of chemotherapy.