胃癌淋巴结转移灶中COX-2和Bcl-2的表达及其与体外化疗敏感性的关系

目的 探讨胃癌淋巴结转移灶中环氧合酶-2(COX-2)和Bcl-2的表达及其与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体外培养化疗药敏性实验,并对原发灶和转移灶行COX-2和Bcl-2免疫组化染色. 结果原发灶中COX-2和Bcl-2强表达率分别为52%和45%,转移灶中分别为72%和60%.COX-2在转移灶中的表达明显高于原发灶(χ~2=4,P<0.05),而Bcl-2在转移灶与原发灶中表达强度相比差异无统计学意义(χ~2=3,P>0.05).在原发灶与转移淋巴结之间COX-2和Bcl-2表达均具有明显相关性(r=0.3403,0.4560,均P<0.05);在原发灶及转移灶中,COX-2与Bcl-2之间表达强度均具有正相关性(r=0.6014,0.5330,均P<0.01).在原发灶中COX-2强表达组的5氟尿嘧啶、长春新碱、表阿霉素对肿瘤细胞的抑制率明显低于弱表达组(t=2.29、2.18、2.41,均P<0.05);Bcl-2强表达时,5氟尿嘧啶、紫杉醇、表阿霉素对肿瘤细胞的抑制率均明显低于弱表达组(t=2.46、2.23、2.22,均P<0.05).在转移淋巴结中,COX-2强表达时长春新碱和甲氨蝶呤对肿瘤细胞的抑制率明显下降(t=2.17、2.35,均P<0.05);Bcl-2强表达组的5氟尿嘧啶、足叶乙甙、紫杉醇和甲氨蝶呤4种药物的抑制率均低于弱表达组(t=2.32、2.29、2.50、2.25,均P<0.05).结论 COX-2和Bcl-2参与了胃癌多药耐药,且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进行.

Relationship between expression of cydooxygenase-2, Bcl-2 and chemosensitivities in lymph node metastases of gastric carcinoma

Objective To investigate the relationship between expression of cyclooxygenase-2 (COX-2), Bcl-2 and chemosensitivities in lymph node metastases (LNMs) of gastric carcinoma. Methods The chemosenisitivities to 9 drugs were measured by MTT assay, and the expression of COX-2, Bcl-2 was determined immunohistochemically in 40 paired primary tumor (PT) and lymph node metastases(LNMs)of gastric carcinoma. Results The positive rate of COX-2 and Bcl-2 in PT were 52.5%, 45.0% respectively, and in LNMs, the positive rate were 72.5% and 60.0%. The expression of COX-2 was higher in LNMs than in PT(χ~2=4, P<0.05). There was no statistically difference in the expression of Bcl-2 between PT and LNMs(χ~2=3, P>0.05). There was positive correlation of COX-2, Bcl-2 between PT and LNMs(r=0.3403, 0.4560, beth P<0.05). There was positive correlation between COX-2 and Bcl-2 in PT and LNMs (r=0.6014, 0.5330, both P<0.01). In PT the inhibition rate for 5-FU, VCR and eADM in COX-2 high expression group were lower than those in low expression group (t=2.29, 2.18, 2.41, all P< 0.05). The inhibition rate to 5-FU, PTX and eADM was significantly lower for the Bcl-2 high expression group in PT (t=2.46, 2.23, 2.22, all P<0.05). In LNMs, there were lower inhibition rates for VCR and MTX in COX-2 strong expression group (t=2.17, 2.35, both P<0.05); the inhibition rates to 5-FU, VP-16, PTX and MTX were significantly lower for the Bcl-2 strong expression group in LNMs (t=2.32, 2.29, 2.50, 2.25, all P<0.05). Conclusions COX-2 and Bcl-2 are involved in MDR of gastric carcinoma. The LNMs of gastric carcinoma are heterogeneous with respect to expression of COX-2, Bcl-2 and response to chemosensitivities. Effective adjuvant chemotherapy in gastric carcinoma depends on targeting the metastatic component of the tumor.