卵巢癌细胞及组织中P38MAPK信号通路调控uPA蛋白的表达及临床意义

P38MAPK Signaling Pathway is Involved in Expression Regulation of uPA Protein in Ovarian Cancer Cells and Tissues

目的探讨P38MAPK信号通路与u PA在卵巢癌细胞及组织中的表达及临床意义。方法应用免疫组织化学法检测u PA、P38MAPK、ERK、AKT蛋白在49例卵巢癌组织中的表达,Western blot检测HO8910及HO-8910PM细胞系中u PA、P38MAPK蛋白的表达,特异性抑制剂SB203580阻断P38MAPK信号通路后u PA蛋白表达水平的变化。结果 u PA、P38MAPK、ERK、AKT蛋白在卵巢癌组织中表达阳性率分别为61.22%、57.14%、53.06%、55.10%。u PA与p38MAPK蛋白表达呈正相关(r=0.8645,P=0.001),且与卵巢癌组织的临床病理分期、分化、转移程度有关(P均<0.05),而与患者的年龄、组织学类型无明显相关(P>0.05)。ERK、AKT蛋白表达与卵巢癌淋巴结转移、大网膜转移有关(P均<0.05),而与患者的年龄、组织类型、病理分期无明显关系(P>0.05)。HO-8910PM细胞系中u PA蛋白的表达水平明显高于HO8910,SB203580阻断P38MAPK信号通路后可降低u PA蛋白的表达,且随着SB203580浓度升高,u PA蛋白表达逐渐降低。P38MAPK及u PA蛋白的表达与卵巢癌的预后显著相关(r=3.897,11.044,P=0.048,0.001)。结论卵巢癌组织中P38MAPK信号通路处于激活状态;该通路的激活可上调u PA的表达,促进卵巢癌的恶性进展;P38MAPK信号通路和u PA可能在卵巢癌侵袭和转移的过程中发挥重要作用。P38MAPK和u PA蛋白有望成为卵巢癌预后评估的重要指标之一。

Objective To explore the expression of P38 MAPK signaling pathway and u PA in ovarian cancer and related clinical significance. Methods The expression of u PA, AKT, ERK and P38 MAPK were detected in 49 cases of ovarian cancer tissues by immunohistochemistry. The expression of u PA and P38 MAPK were detected by Western blot in ovarian cancer cell lines HO8910 and HO-8910 PM. We detected the change of u PA protein expression after P38 MAPK signal pathway was cut off by SB203580 specific inhibitor. ResultsImmunohistochemical method results showed that the positive expression rates of u PA, P38 MAPK, ERK and AKT protein were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of u PA was positively correlated with P38MAPK(r=0.8645, P=0.001), and was related with clinicopathologic stage, differentiated degree, lymph node metastasis(all P<0.05), but not related with age or histologic type(P>0.05). The expression of AKT and ERK were related with lymph node metastasis and greater omentum metastasis(P<0.05), but not related with age, histologic type or clinicopathologic stage(P>0.05). The expression of u PA in HO-8910 PM cell line was higher than that in ovarian cancer cell lines HO8910, and the expression of u PA was decreased when P38 MAPK signal pathway was cut off by SB203580, in a concentration-dependent manner. The expression of P38 MAPK and u PA were significantly correlated to the prognosis of ovarian cancer patients(r=3.897, 11.044, P=0.048, 0.001). Conclusion P38 MAPK signal pathway is activated in ovarian cancer tissues. The activated p38 MAPK signal pathway could upregulate the expression of u PA, which may contribute to the development of ovarian cancer. P38 MAPK signal pathway and u PA may play an important role in the invasion and metastasis of ovarian cancer. P38 MAPK and u PA might help to evaluate the prognosis of ovarian cancer patients.