胃癌淋巴结转移灶COX-2与P-gp、生存素表达及体外化疗药物敏感性的关系

Relationship between expressions of cyclooxygenase-2,P-gp,survivin and chemosensitivities in lymph node metastases of gastric carcinoma

目的探讨胃癌淋巴结转移灶环氧合酶2(COX-2)与多药耐药(MDR)因子P-糖蛋白(P-gp)、生存素表达及体外化疗敏感性的关系。方法对40例胃癌新鲜肿瘤组织及转移淋巴结进行肿瘤细胞培养化疗药敏性实验,并对原发灶、淋巴结转移灶行COX-2、P-gp及生存素免疫组化染色。结果COX-2在胃癌原发灶、淋巴结转移灶中表达一致率为30%(P>0.05),但在转移灶中的表达高于原发灶(P<0.05)。在胃癌原发灶及淋巴结转移灶中COX-2与生存素表达均呈正相关(P<0.05);在淋巴结转移灶中COX-2与P-gp表达呈正相关(P<0.05)。9种化疗药物中,VCR、OPT、DDP对转移淋巴结肿瘤细胞抑制率均低于原发灶(P<0.05),仅VP-16对原发灶的抑制率明显低于转移灶(P<0.05)。胃癌原发灶COX-2表达与5-FU、OPT的抑制率呈负相关(P<0.05);在淋巴结转移灶中,COX-2表达与VP-16、OPT和eADM的抑制率呈负相关(P<0.05)。结论COX-2参与了胃癌多药耐药,且其在淋巴结转移灶中的表达及化疗药敏性均呈现与原发灶不同的异质性,术后辅助化疗应针对淋巴结转移灶。

Objective To investigate the relationship of the expressions of cyclooxygenase-2 （COX-2）, P-glycoprotein（P-gp） and survivin with the chemosensitivities of gastric carcinoma with lymph node metastases （LNMs） in vitro. Methods The chemosenisitivities to 9 kinds of drugs were measured by MTT assay, and the expressions of COX-2, Pgp and survivin were determined immunohistochemically in 40 paired primary tumors（PT） and LNMs of gastric carcinoma. Results The accordance rate of COX-2 expression was 300/00 betwen PT and LNMs （P〉0.05）. The expression of COX-2 was higher in LNMs than that in PT （P〈0.05）. The expression of COX-2 in PT and LNMs was positively correlated with survivin （P〈0.01）. There was a positive correlation between COX-2 and P-gp in LNMs （P〈0.05）. The inhibition rate of LNMs cells for VCR,OPT or DDP was lower than that of PT （P〈 0.05）, which only for VP-16 was higher （P〈 0. 05）. There was a statistically negative correlation between the expression of COX-2 and inhibition rate of PT for 5 FU or OPT （P〈0.05）, and of LNMs for VP-16, OPT or eADM （P〈0.05）. Conclusion COX-2 takes part in multiple drug resistance（MDR） of gastric carcinoma. The expression and chemosensitivitiy of COX2 in LNMs of gastric carcinoma are different from those in PT. Effective adjuvant chemotherapy in gastrointestinal cancers should be focused on the metastatic components of the tumor.