胃癌转移淋巴结奥沙利铂体外化疗药敏性与多种耐药相关因子表达的关系

目的:探讨胃癌淋巴结转移灶肿瘤细胞对奥沙利铂的体外化疗药敏性与多种多药耐药相关因子表达的关系.方法:分离提取54例胃癌新鲜肿瘤组织及转移淋巴结中的肿瘤细胞,进行肿瘤细胞培养化疗药敏性实验,同时用免疫组织化学法检测原发灶、淋巴结转移灶多药耐药相关因子P-gp、GST-π、p53、Survivin和Bcl-2的表达.结果:奥沙利铂对胃癌淋巴结转移灶肿瘤细胞的抑制率低于原发灶(P<0.05).P-gp、GST-π和Bcl-2在淋巴结转移灶中表达程度均高于原发灶(P均<0.05),而p53和Survivin在肿瘤原发灶、转移灶中的表达强度无显著性差异(P均>0.05);P-gp、p53、Bcl-2表达在胃癌原发灶、淋巴结转移灶中均呈正相关(γ分别为0.3424、0.7123、0.4548,P均<0.05),而GST-π、Survivin在两种组织间表达强度无明显相关性(P均>0.05).胃癌原发灶奥沙利铂对肿瘤细胞的药物抑制率与P-gp、GST-π和Survivin表达强度呈负相关(P均<0.05),三者对药物抑制率影响作用依次为GST-π>P-gp>Survivin;转移淋巴结中仅发现Survivin表达强度对药物抑制率有影响,与药物抑制率呈负相关(P<0.05).结论:胃癌淋巴结转移灶中,奥沙利铂对肿瘤细胞抑制率和多药耐药相关因子的表达均显示出与原发灶不同的异质性变化,肿瘤原发灶与转移灶中影响奥沙利铂药敏性的主要因子也不相同,术后辅助化疗及实现多药耐药逆转应针对淋巴结转移灶进行.

Relationship between Chemosensitivity to L-OHP in vitro and Expressions of Multidrug Resistance Associated Factors in Lymph Node Metastases of Gastric Carcinoma

Objective: To investigate the relationship between chemosensitivity to L-OHP and expressions of multidrug resistance (MDR) associated factors in lymph node metastases (LNMs) of gastric carcinoma. Methods: The chemosensitivity to L-OHP was measured by MIT assay, and the expressions of P-gp, GST-π, P53, Survivin and Bcl-2 were determined by immunohistochemistry in 54 paired primary tumor (PT) and LNMs of gastric carcinoma. Results: The inhibition rates of LNMs cells for L-OHP were lower than those of PT (P<0.05). The expressions of P-gp, GST-π and Bcl-2 were higher in LNMs than in PT (P<0.05), and no signifi-cant difference was found in the expression of P53 and Survivin between LNMs and PT (P>0.05). Positive cor-relations among P-gp, P53 and Bcl-2 were found in PT and LNMs (r=0.3424, 0.7123, 0.4548, P<0.05). There was no significant difference in the expression of GST-π and Survivin between PT and LNMs (P>0.05). There was statistically negative correlation between inhibition rates and expression of P-gp, GST-π, and Survivin in PT (P<0.05). In LNMs, only Survivin was negatively correlated with inhibition rates of L-OHP (P<0.05). Conclu-sion: The LNMs of gastric carcinoma are heterogeneous with PT in respect to chemosensitivity to L-OHP and expression of multidrug resistance associated factors. The main factors that affect chemosensitivity to L-OHP are also significantly different between PT and LNMs. Effective adjuvant chemotherapy after surgery and re-version to multidrug resistance (MDR) of gastric carcinoma depend on targeting the metastatic lesions of gas-tric carcinoma.