目的:检测Dyrk1B在上皮性卵巢癌组织和细胞中的表达,探讨其在卵巢癌发生和发展中的作用及意义。方法:Western blot法检测卵巢癌细胞系(OVCAR8,OVCAR5,OVCAR4,OVCAR3,SKOV3,OV2008,C13,A2780S和A2780CP)中Dyrk1B蛋白表达,以及Dyrk1B抑制剂AZ191对卵巢癌细胞Dyrk1B蛋白表达的影响。MTT比色法和流式细胞术检测AZ191对卵巢癌细胞增殖能力和细胞凋亡的影响。选取我院近7年收治的上皮性卵巢癌患者119例,免疫组化SP法检测Dyrk1B蛋白在卵巢癌组织中的表达。结果:Dyrk1B蛋白在多种卵巢癌细胞系中普遍表达,AZ191可明显降低其在卵巢癌细胞中的表达;AZ191对各种卵巢癌细胞系的增殖能力均产生浓度依赖性的抑制作用(P〈0.05),并可诱发细胞凋亡,其凋亡率均随抑制剂浓度的增加而增高;Dyrk1B在卵巢癌组织中亦呈高表达,表达率为90.8%。结论:Dyrk1B在上皮性卵巢癌组织和细胞中均有表达,Dyrk1B抑制剂AZ191下调卵巢癌细胞Dyrk1B蛋白表达的同时,明显抑制细胞的增殖和诱发细胞凋亡。提示Dyrk1B可能在卵巢癌的发生和发展中起关键作用,有望成为临床分子靶向治疗卵巢癌的新靶点。
Objective:To examine the expression of Dyrkl B in the specimens and cells of epithelial ovarian cancer,and to explore the role of DyrklB in the occurrence and development of ovarian cancer. Methods: Dyrkl B protein was determined by Western blot in ovarian cancer cells treated with/without Dyrkl B inhibitor,AZ191. The cellular proliferation and apoptosis of ovarian cancer cells after 48h-treatment of AZ191 were analyzed by MTT assay and Flow cytometry,respectively. Immunohistochemistry was utilized to detect DyrklB expression in the specimens of 119 cases of epithelial ovarian cancer,which was included 77 cases of serous carcinoma,17 cases of mucinous carcinoma, 15 cases of endometrial carcinoma, and 10 cases of clear cell carcinoma. Results: DyrklB was widely overexpressed in vary kinds of cell lines of OVCARS, OVCAILS, OVCAR4, OVCAR3, SKOV3, OV2008, C13, A2780S, and A2780CP. Dyrkl B protein of the ovarian cancer cells was significantly reduced by Western blot after 48htreatment of AZ191. The cellular proliferation was significantly inhibited and cell apoptosis of oarian cancer cells analyzed by Flow cytometry was significantly increased after 48h-treatment of AZ191 in a concentration-dependent manner (P 〈0.05 ). The immunohistochemical results showed that Dyrkl B was overexpressed in the specimens of ovarian cancer with the expression rate 90.8% (108/119), compared with normal ovarian tissue with the expression rate 15.7% (3/19) ,which exhibited statistically significant difference (P = 0. 001 ). Conclusion: DyrklB is overexpressed in both the specimens and cells of epithelial ovarian cancer. AZ191 ,an inhibitor of Dyrkl B, can inhibit cellular proliferation and induce apoptosis of ovarian cancer cells accompanied by decreased DyrklB protein expression. All together, our study suggests that Dyrkl B may play an important role in the tumorigenesis and development of ovarian cancer, and it may serve as important therapeutic target for the patients.