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

目的 探讨P38MAPK信号通路与uPA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uPA、P38MAPK、ERK、AKT蛋白在49例卵巢癌组织中的表达，Westernblot检测HO8910及HO-8910PM细胞系中uPA、P38MAPK蛋白的表达，特异性抑制剂SB203580阻断P38MAPK信号通路后uPA蛋白表达水平的变化。结果 uPA、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%。uPA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uPA蛋白的表达水平明显高于HO8910，SB203580阻断P38MAPK信号通路后可降低uPA蛋白的表达，且随着SB203580 浓度升高，uPA蛋白表达逐渐降低。P38MAPK及uPA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uPA的表达，促进卵巢癌的恶性进展；P38MAPK信号通路和uPA可能在卵巢癌侵袭和转移的过程中发挥重要作用。P38MAPK和uPA蛋白有望成为卵巢癌预后评估的重要指标之一。

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

Objective To explore the expression of P38 MAPK signaling pathway and uPA in ovarian cancer and related clinical significance. Methods The expression of uPA, AKT, ERK and P38MAPK were detected in 49 cases of ovarian cancer tissues by immunohistochemistry. The expression of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910 and HO-8910PM. We detected the change ofuPA protein expression after P38MAPK signal pathway was cut off by SB203580 specific inhibitor. Results Immunohistochemical method results showed that the positive expression rates of uPA, P38MAPK, ERK and AKT protein were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of uPA 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 uPA in HO-8910PM cell line was higher than that in ovarian cancer cell lines HO8910, and the expression of uPA was decreased when P38MAPK signal pathway was cut off by SB203580, in a concentration-dependent manner.The expression of P38MAPK and uPA were significantly correlated to the prognosis of ovarian cancer patients(r=3.897, 11.044, P=0.048, 0.001). Conclusion P38MAPK signal pathway is activated in ovarian cancer tissues. The activated p38MAPK signal pathway could upregulate the expression of uPA, which may contribute to the development of ovarian cancer. P38MAPK signal pathway and uPA may play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might help to evaluate the prognosis of ovarian cancer patients.