贫血对胃癌患者术后化疗耐药的影响

Effect of anemia on chemotherapy multidrug resistance in postoperative of gastric cancer

目的本研究通过检测P-糖蛋白(P-glycoprotein,P-gp)、拓扑异构酶-Ⅱ(topoisomerase-Ⅱ,TOPO-Ⅱ)、谷胱甘肽转移酶-π(glutathione-S-transferase-π,GST-π)及缺氧诱导因子-1α(hypoxia-induciblefactor-1α,HIF-1α)在胃癌组织中的表达情况,探讨贫血在胃癌术后化疗肿瘤的多药耐药[1](multidrugresistance,MDR)中的影响及其可能的内在机制。方法采用免疫组化SupervisionTM二步法检测56例胃癌组织及20例癌旁正常组织中P-gp、TOPO-Ⅱ、GST-π的表达,采用SABC法对检测上述组织中HIF-1α蛋白的表达。结果①胃癌组织P-gp、GST-π、HIF-1α表达水平高于癌旁正常组织,TOPO-Ⅱ表达水平低于癌旁正常组织。②P-gp、GST-π在不同组织学类型之间有显著性差异,HIF-1α在不同癌肿浸润深度及有、无淋巴结转移之间有显著性差异。P-gp、TOPO-Ⅱ、GST-π、HIF-1α表达水平与年龄、性别之间无关。③在胃癌组织中,P-gp、GST-π及HIF-1α表达水平与Hb成正相关,TOPO-Ⅱ表达水平与Hb成负相关,且HIF-1α与P-gp表达水平之间成正相关。结论胃癌患者术后化疗MDR与贫血成正相关,HIF-1α可能是贫血导致胃癌患者术后化疗MDR的介导因子之一。

Object This study was designed to investgate the expression of P - glycoprotein （ P - gp）, topoisomerase - Ⅱ （TOPO - Ⅱ ） , glutathione - S - 1 α （ HIF - 1α） in gastric cancer and the effect and transferase - π （ GST - π ） and hypoxia - inducible factor - possible mechanism of anemia on chemotherapy multidrug resistance in postoperative of gastric cancer. Methods 56 cases of tissue samples of gastric cancer and 20 cases of pericarcinoma normal tissue samples were examined for expression of P - gp, TOPO - Ⅱ , GST - π and HIF - 1α by immunohistochemistry. Results （1）The expression levels of P - gp, GST - π and HIF - 1α in gastric cancer were significantly higher than pericareinoma normal tissues, however, the expression level of TOPO - Ⅱ ingastric cancer was significantly lower than pericarcinoma normal tissues. ②The expression levels of P-gp、GST- π were significantly different in histological types, the expression level of HIF - 1α was signifi of P - gp, GST candy different in depth of invasion or with and without lymph nodes metastasis. There was no correlation between the expression of them and sexual or age. ③In gastric cancer, the expression levels of P - gp,GST - π and HIF - 1α were positive correlation with Hb concentration, the TOPO - Ⅱ was negative correlation with Hb, evenmore, the expression level of HIF - 1α was positive correlation with the P - gp. Conclusion The chemotherapy muhidrug resistance in postoperative of gastric cancer is positive correlation with anemia degree, HIF - 1α maybe one of the inducible factors which lead anemia to chemotherapy muhidrug resistance in postoperative of gastric cancer.