SLC4A11通过JAK信号通路对卵巢癌细胞增殖、迁移和侵袭的影响

Influence of solute carrier family 4 member 11 on the proliferation,migration,and invasion of ovarian cancer cell through JAK signaling pathway

目的:探讨溶质转运家族4成员11蛋白(SLC4A11)在卵巢癌增殖、迁移和侵袭中的生物学作用机制。方法:RT-qPCR检测卵巢癌细胞中SLC4A11表达。将SKOV3细胞分为对照组(转染siRNA-NC序列)、SLC4A11-siRNA组(干扰SLC4A11表达)和SLC4A11-siRNA+JAK组(干扰SLC4A11表达+激活JAK信号通路)。采用CCK-8、伤口愈合实验和Transwell实验检测细胞的增殖、迁移和侵袭能力。RT-qPCR和Western blot检测Janus激酶2(JAK2)和信号传导及转录激活因子3(STAT3)、B细胞淋巴瘤2(Bcl-2)表达。结果:SLC4A11在卵巢癌组织中高表达(P<0.05)。SLC4A11-siRNA组SKOV3细胞中p-JAK2/JAK2(0.286±0.048)、p-STAT3/STAT3(0.571±0.042)、Bcl-2(0.335±0.040)均低于对照组(1.001±0.093、1.004±0.089、1.005±0.142),也低于SLC4A11-siRNA+JAK组[p-JAK2/JAK2(1.001±0.095)、p-STAT3/STAT3(1.003±0.092)和Bcl-2(1.006±0.145)];SKOV3细胞活力SLC4A11-siRNA组(1.112±0.113)、SLC4A11-siRNA+JAK组(1.612±0.113)、对照组(1.778±0.167)依次升高,SKOV3细胞划痕愈合率SLC4A11-siRNA组(21.927±3.279)、SLC4A11-siRNA+JAK组(54.763±6.794)、对照组(56.787±10.985)依次升高,侵袭细胞数量SLC4A11-siRNA组(68.000±5.568)、SLC4A11-siRNA+JAK组(172.667±4.041)、对照组(184.667±14.640)依次升高(均P<0.01)。结论:SLC4A11可能通过调控抑制JAK/STAT3信号通路参与卵巢癌进展,提示SLC4A11可能成为卵巢癌潜在治疗靶点。

Objective:To explore the biological mechanism of solute carrier family 4 member 11(SLC4A11) in the proliferation,migration,and invasion of ovarian cancer cell.Methods:RT-qPCR was performed to detect the expression level of SLC4A11 in ovarian cancer cells.SKOV3 cells were divided into control group(transfected with siRNA-NC),SLC4A11-siRNA group(disturbed the expression of SLC4A11),and SLC4A11-siRNA+JAK group(disturbed the expression of SLC4A11 + activation of JAK pathway).CCK-8,Wound-healing assay,and transwell assay were carried out to detect the proliferation,migration,and invasion abilities of the cells.RT-qPCR and Western blot were performed to analyze the expression levels of Janus-Activated Kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),and B-cell lymphoma-2(Bcl-2) of the cells.Results:High SLC4A11 expression was found in ovarian cancer tissues,and which was negatively associated with the adverse overall survival(OS) of the patients with ovarian cancer(P<0.05).The levels of p-JAK2/JAK2(0.286±0.048),p-STAT3/STAT3(0.571±0.042),and Bcl-2(0.335±0.040) of SKOV3 cells in SLC4A11-siRNA group were significantly lower than those(1.001±0.093,1.004±0.089,and 1.005±0.142) of SKOV3 cells in the control group,and which was also significantly lower than those(1.001±0.095,1.003±0.092,and 1.006±0.145) of SKOV3 cells in SLC4A11-siRNA+JAK group.The viability of SKOV3 cell in SLC4A11-siRNA group(1.112±0.113),in SLC4A11-siRNA+JAK group(1.612±0.113),and in the control group(1.778±0.167)had increased gradually.The scratch healing rate of SKOV3cells in SLC4A11-siRNA group(21.927±3.279),in SLC4A11-siRNA+JAK group(54.763±6.794),and in the control group(56.787±10.985)had increased gradually.The number of the invasive cells in SLC4A11-siRNA group(68.000±5.568),in SLC4A11-siRNA+JAK group(172.667±4.041),and in the control group(184.667±14.640)had increased gradually(all P<0.01).Conclusion:SLC4A11might involve in the development of ovarian cancer by regulating restrain JAK/STAT3signaling pathway,and which suggest that SLC4A11can be as a therapeutic target of the ovarian cancer.