王亚萍 余军辉 王凯

[关键词] 卵巢癌;肌动蛋白相关蛋白复合体2;迁移;Wnt/β-catenin通路

[中图分类号] R737.3          [文献标识码] A          [文章编号] 1673-9701（2021）19-0038-06

Down-regulation of ARPC2 reducing the malignant metastatic potential of ovarian cancer OVCA429 cells by inhibiting Wnt/β-catenin pathway

WANG Yaping   YU Junhui   WANG Kai

Department of Gynecology， Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University， Taizhou   318050， China

[Abstract] Objective To investigate the effect and mechanism of down-regulation of actin-related protein complex 2 （ARPC2） on the malignant metastatic potential of ovarian cancer OVCA429 cells. Methods The changes of APC2 expression in ovarian cancer Skov3，A2780，OVCA429 cells，and normal ovarian IOSE386 cells were detected by qRT-PCR and Western blot.Arpc2 siRNA was transfected into ovarian cancer OVCA429 cells.Cell proliferation was determined by MTT.Cell migration and invasion were detected by the Transwell chamber. The ARPC2，β-catenin，c-myc，MMP-9，MMP-2 protein expression in cells were detected by Western blot.The ovarian cancer OVCA429 cells transfected with APC2 siRNA were treated with the Wnt/β-catenin activator LiCl.Cell proliferation，migration，and invasion changes were also measured by the above method. Results The expression level of ARPC2 in ovarian cancer Skov3，A2780，and OVCA429 cells was significantly higher than that of normal ovarian IOSE386 cells.The expression level of ARPC2 was the highest in ovarian cancer OVCA429 cells. After the transfection of APC2 siRNA，the proliferation ability of ovarian cancer OVCA429 cells decreased，and the cell migration and invasion ability also decreased.The expression of APC2，β-catenin，c-myc，MMP-9，MMP-2 protein in the cells decreased. The Wnt/β-catenin activator LiCl can reverse the inhibitory effects of APC2 siRNA on the proliferation，migration，and invasion of ovarian cancer OVCA429 cells. Conclusion Down-regulation of APC2 reduces the malignant metastatic potential of ovarian cancer OVCA429 cells by inhibiting the activation of Wnt/β-catenin pathway.

[Key words] Ovarian cancer;Actin-related protein complex 2;Migration;Wnt/β-catenin pathway

卵巢癌是臨床上常见的恶性肿瘤之一，其恶性程度高、转移能力强，很多卵巢癌患者在确诊时已经发生了远处转移，给卵巢癌的治疗带来了巨大挑战[1]。研究显示，卵巢癌的发生是一个基因异常表达的过程，卵巢癌组织有着与正常组织不同的基因表达谱，这些基因可能是卵巢癌治疗的分子靶点[2]。肌动蛋白相关蛋白复合体2（Actin-related protein complex2，ARPC2）是一个具有调控细胞骨架运动和构成的肌动蛋白相关蛋白2/3（Actin-related protein 2/3，Arp2/3）复合物的亚基之一，ARPC2在人体组织中表达，参与调控细胞生长、侵袭等过程[3]。ARPC2还参与人类多种疾病发生，ARPC2在乳腺癌、胃癌等肿瘤组织中表达上调，下调ARPC2抑制肿瘤细胞侵袭和迁移，ARPC2可能是一种癌基因[4-5]。Wnt/β-catenin在人体内普遍存在，其在肿瘤进展中过度激活，β-catenin表达上调后可以诱导下游基因c-myc的激活，促进肿瘤进展[6]。Arp 2/3复合物介导的肌动蛋白聚合反应可被Wave复合物激活，从而实现细胞扩散，迁移，粘附和分裂。其中，Wave复合物在Wnt /β-catenin途径中具有调节功能[7]。