摘要
背景与目的:P-糖蛋白(P-gp)介导的经典耐药途径和细胞凋亡抑制是肿瘤多药耐药(MDR)研究最多的两种机制,肿瘤细胞多种MDR相关基因/蛋白共同表达、相互作用而出现多态性耐药。本研究通过分析肿瘤P-gp和凋亡抑制蛋白p53、Survivin、bcl-2表达与化疗药敏性的关系,探讨消化道肿瘤组织MDR相关因子表达能否反映肿瘤的化疗耐药性。方法:84例胃癌、大肠癌标本进行MTT法体外化疗药物敏感性实验,免疫组化染色检测组织中P-gp、p53、Survivin、bcl-2的表达,分析4种多药耐药相关因子表达与9种药物对肿瘤细胞抑制率的关系。结果:肿瘤组织中P-gp、p53、Survivin、bcl-2表达率分别为96.4%、64.3%、89.3%、60.7%;P-gp与bcl-2表达、Survivin与bcl-2表达具有正相关性(r=0.5072,r=0.3027,P<0.05)。在肿瘤组织耐药因子表达程度与药物对肿瘤细胞抑制率的关系中,P-gp强表达组PTX、OXA、DDP对肿瘤细胞的抑制率明显低于弱表达组(P<0.05);p53强表达与PTX、DDP对肿瘤细胞的抑制率明显降低有关(P<0.05);Survivin强表达时,VCR、DDP对肿瘤细胞的抑制率明显降低(P<0.05),但OXA对肿瘤细胞的抑制率明显增加(P<0.01);bcl-2强表达时,5-FU、VCR、EADM、OXA对肿瘤细胞的抑制率明显低于弱表达组(P<0.05)。结论:消化道肿瘤P-gp、p53、Survivin、bcl-2表达程度仅与其对部分化疗药物的耐药性有关,评价消化道肿瘤组织某种耐药因子表达与化疗药物耐药性的关系必须考虑多种因素调节的影响。
BACKGROUND ＆ OBJECTIVE. P-glycoprotein （P-gp） mediated classical drug resistance and inhibition of the apoptotic pathway are the two mostly investigated mechanisms of multidrug resistance （MDR）. Coexpression and interaction of MDR-related factors result in pleiotropic drug resistance in cancer cells. This study was to investigate the correlation of expressions of multiple MDR-related factors, such as P-gp, p53, Survivin or bcl-2, to chemosensitivitity in gastrointestinal carcinomas. METHODS. Eighty-four tissue specimens of gastrointestinal carcinomas were analyzed. Expressions of P-gp, p53, Survivin and bcl-2 were determined by immunohistochemistry （IHC）. Drug chemosensitivity of nine drugs to cancer cells were measured by MTT assay. RESULTS： The positive staining of P- gp, p53, Survivin and bcl-2 were detected in 96.4%, 64.3%, 89.3% and 60.7% of all specimens, respectively. The expression of P-gp and bcl-2 （r= 0.5072, P〈0.05）, and the expression of survivin and bcl-2 （r=0.3027, P〈 0.05） were positively correlated. The inhibition rates of paclitaxel （PTX）, oxaliplatin （OXA） or cisplatin （DDP） on cancer cells were significantly lower in the group with strong P-gp expression than that with weak P-gp expression （all P〈0.05）. The strong expression of p53 was correlated with decreased inhibition rates of PTX and DDP on cancer cells （P〈0.05, P〈 0.01）. When the expression of Survivin was increased, the inhibition rates of vincristine （VCR） or DDP on cancer cells were reduced significantly （P〈 0.05, P〈0.01）, but the inhibitory effect of OXA was remarkably increased （P〈0.01）. The inhibition rates of 5-fluorouracil （5-FU）, VCR, epirubicin （EADM） and OXA on cancer cells were lower in the group with strong expression of bcl-2 than in that with weak expression of bcl-2 （P〈0.05）. CONCLUSIONS. The expression of MDR-related factors in gastrointestinal carcinomas is associated with drug resistance of only certain chemotherapy drugs. Multiple factors and mechanisms should be considered when assessing the influence of MDR related factors on drug resistance.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2008年第11期1166-1171,共6页
Chinese Journal of Cancer
基金
河北省科技计划项目(No.06276102D-73)~~
关键词
消化道肿瘤
多药耐药性
凋亡抑制蛋白
P-糖蛋白
体外药敏实验
Gastrointestinal neoplasm
Multidrug resistance
Inhibitor ofapoptosis proteins
P-glycoprotein
Chemosensitivity test
