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目的研究残疾基因同源物2(DAB2)相互作用蛋白(DAB2IP)在人膀胱癌组织中的表达并分析与肿瘤病理分级、临床分期的相关性,同时观察DAB2IP与膀胱癌化疗耐药的关系。方法通过免疫组织化学染色方法检测初发和复发膀胱癌中DAB2IP的表达差异。应用RNA干涉(RNAi)技术敲低5637和253J膀胱癌细胞中DAB2IP的表达后,采用MTT法、克隆形成实验验证癌细胞对吡柔比星的敏感性的变化,流式细胞术检测吡柔比星处理后DAB2IP低表达细胞的凋亡率。结果 DAB2IP的表达与膀胱癌TNM分期、病理分级及淋巴结转移等负相关,复发的膀胱癌组织DAB2IP的表达低于初发膀胱癌组织。DAB2IP的低表达与膀胱癌细胞抗药性相关,敲低DAB2IP的水平增强膀胱癌细胞的集落形成能力,促凋亡蛋白PARP和caspase-3表达减少,抑制凋亡蛋白Bcl-2和Mcl-1的表达增加,癌细胞凋亡能力降低、引起化疗耐受。结论敲低DAB2IP的水平可促进膀胱癌细胞的增殖并抑制凋亡,同时增强其化疗耐受性。
Objective To study the expression of DAB2IP in human bladder cancer and to analyze the relationship between the expression of DAB2IP and tumor grade and clinical stage, and to observe the relationship between DAB2IP and chemoresistance in bladder cancer. Methods The expression of DAB2IP in primary and recurrent bladder cancer was detected by immunohistochemical staining. After the expression of DAB2IP in 5637 and 253J bladder cancer cells was knocked down by RNA interference (RNAi) technology, the sensitivity of the cancer cells to pirarubicin was tested by MTT assay and colony formation assay. The results of flow cytometry Apoptotic rate of DAB2IP low expressing cells after star treatment. Results The expression of DAB2IP was negatively correlated with TNM staging, pathological grading and lymph node metastasis in bladder cancer. The expression of DAB2IP was lower in primary bladder cancer than in primary bladder cancer. The low expression of DAB2IP is associated with drug resistance in bladder cancer cells. Knockdown of DAB2IP enhances the colony-forming ability of bladder cancer cells, decreases the expression of pro-apoptotic proteins PARP and caspase-3, and inhibits the expression of apoptotic proteins Bcl-2 and Mcl-1 Increased expression, reduced ability of cancer cells to apoptosis, causing chemotherapy tolerance. Conclusion Knocking down the level of DAB2IP can promote the proliferation and inhibit the apoptosis of bladder cancer cells and enhance its chemoresistance.