下調(diào)ARPC2通過抑制Wnt/β-catenin通路激活水平降低卵巢癌OVCA429細(xì)胞惡性轉(zhuǎn)移潛能

王亞萍 余軍輝 王凱

[關(guān)鍵詞] 卵巢癌;肌動蛋白相關(guān)蛋白復(fù)合體2;遷移;Wnt/β-catenin通路

[中圖分類號] R737.3? ? ? ? ? [文獻(xiàn)標(biāo)識碼] A? ? ? ? ? [文章編號] 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

卵巢癌是臨床上常見的惡性腫瘤之一，其惡性程度高、轉(zhuǎn)移能力強(qiáng)，很多卵巢癌患者在確診時(shí)已經(jīng)發(fā)生了遠(yuǎn)處轉(zhuǎn)移，給卵巢癌的治療帶來了巨大挑戰(zhàn)[1]。研究顯示，卵巢癌的發(fā)生是一個(gè)基因異常表達(dá)的過程，卵巢癌組織有著與正常組織不同的基因表達(dá)譜，這些基因可能是卵巢癌治療的分子靶點(diǎn)[2]。肌動蛋白相關(guān)蛋白復(fù)合體2（Actin-related protein complex2，ARPC2）是一個(gè)具有調(diào)控細(xì)胞骨架運(yùn)動和構(gòu)成的肌動蛋白相關(guān)蛋白2/3（Actin-related protein 2/3，Arp2/3）復(fù)合物的亞基之一，ARPC2在人體組織中表達(dá)，參與調(diào)控細(xì)胞生長、侵襲等過程[3]。ARPC2還參與人類多種疾病發(fā)生，ARPC2在乳腺癌、胃癌等腫瘤組織中表達(dá)上調(diào)，下調(diào)ARPC2抑制腫瘤細(xì)胞侵襲和遷移，ARPC2可能是一種癌基因[4-5]。Wnt/β-catenin在人體內(nèi)普遍存在，其在腫瘤進(jìn)展中過度激活，β-catenin表達(dá)上調(diào)后可以誘導(dǎo)下游基因c-myc的激活，促進(jìn)腫瘤進(jìn)展[6]。Arp 2/3復(fù)合物介導(dǎo)的肌動蛋白聚合反應(yīng)可被Wave復(fù)合物激活，從而實(shí)現(xiàn)細(xì)胞擴(kuò)散，遷移，粘附和分裂。其中，Wave復(fù)合物在Wnt /β-catenin途徑中具有調(diào)節(jié)功能[7]。