胃癌组织多药耐药与血红蛋白和缺氧诱导因子-1α表达的相关性研究

Correlation study between postoperative multidrug resistance and hemoglobin concentration and the expression of hypoxia-inducible factor-Iαin gastric cancer

目的通过检测P-糖蛋白（P-gp）、拓扑异构酶-Ⅱ（TOPO-Ⅱ）、谷胱甘肽转移酶-π（GST-π）及缺氧诱导因子-1α（HIF-1α）在胃癌组织中的表达，探讨胃癌患者术后化疗多药耐药（MDR）与血红蛋白（Hb）浓度、HIF-1α表达水平的相关性及其可能的内在机制。方法采用免疫组化方法检测56例胃癌组织及20例癌旁正常组织中P-gp、TOPO-Ⅱ、GST-π及HIF-1α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（P〈0．05）。（2）Pgp、GST-π在不同组织学类型之间差异有统计学意义，HIF-1α在不同癌肿浸润深度及有、无淋巴结转移之间差异有统计学意义（P〈0．05）。（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呈负相关，HIF-1α与P-gp表达水平之间呈正相关。结论胃癌患者术后化疗MDR与Hb浓度、HIF-1α表达水平成正相关，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。

Objective To detect the expression of P-glycoprotein （P-gp）, topoisomerase-Ⅱ （TOPO-Ⅱ）, glutathione-S-transferase-π （GST-π） and hypoxia-inducible factor-1 alpha（ HIF-1 alpha） in gastric cancer and to investigate the correlation and possible mechanism between postoperative multidrug resistance（MDR） and hemoglobin（Hb） concentration and the expression of HIF-1α in gastric cancer. Methods Fifty-six tissue samples of gastric cancer and twenty pericarcinoma normal tissue samples were examined for expression of P-gp, TOPO-Ⅱ, GST-π and HIF-1αby 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 in gastric cancer was significantly lower than that in pericarcinoma normal tissues（ P 〈0. 05）. （2）The expression levels of P-gp,GST-π were significantly different in histological types, the expression lev- el of HIF-1α was significantly different in depths of invasion or with and without lymph nodes metastasis（ P 〈 0. 05 ）. （3）In gastric cancer, the expression levels of P-gp, GST-π and HIF-1α were positively correlated with Hb concentration, the TOPO-Ⅱ was negatively correlated with Hb. Furthermore, the expression level of HIF-1α was positively correlated with the P-gp. Conclusion The chemotherapy multidrug resistance in postoperative of gastric cancer is positively correlated with Hb concentration and the expression of HIF-1α. HIF-1α maybe one of the inducible factors which could lead to chemotherapy postoperative multidrug resistance in gastric cancer from anemia.