敲低DAB2相互作用蛋白(DAB2IP)促进膀胱癌细胞增殖并抑制其凋亡

Knock-down of DAB2 interacting protein(DAB2IP) promotes proliferation and inhibits apoptosis of bladder cancer cells

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 DAB2 interacting protein （DAB21P） in human bladder cancer tissues and analyze its relationship with pathological grade and clinical stage, and observe its role in drug resistance of bladder cancer cells. Methods The expression of DAB21P in primary and recurrent bladder cancers was detected by immunohistochemical staining. RNA interference （RNAi） technique was used to down-regulate the expression of DAB21P in 5637 and 253J bladder cancer ceils. MTT assay and clone formation assay were performed to test the sensitivity of cancer cells to pirarubicin. Flow cytometry was done to detect the apoptosis rate of low-DAB21P-expressing cells treated with pirarubicin. Results The expression of DAB21P was negatively correlated with TNM stage, pathological grade and lymph node metastasis of bladder cancer. The expression of DAB21P in the recurrent bladder cancer was lower than that in the primary bladder cancer. The low expression of DAB21P in bladder carcinoma cells was related to drug resistance. Knock-down of DAB21P enhanced the colony formation of bladder cancer cells, reduced the expressions of PARP and caspase-3, increased expressions of Bcl-2 and Mcl-1, reduced the apoptosis of cancer ceils and induced chemotherapy tolerance. Conclusion Knock-down of DAB21P can promote the proliferation and inhibit the apoptosis of bladder cancer cells, and increase the resistance to chemotherapy.