P38MAPK信号通路对卵巢癌中尿激酶型纤维蛋白酶原激活剂的影响

Effects of P38 mitogen-activated protein kinase signal pathway on the expression of urokinase-type plasminogen activator in ovarian cancer

目的探讨卵巢癌细胞及组织中分子量为38 k D的促分裂素原活化蛋白激酶(P38MAPK)信号通路对尿激酶型纤维蛋白酶原激活剂(u PA)的影响。方法应用免疫组化SP法检测49例卵巢癌组织中u PA、P38MAPK、细胞外信号调节激酶(ERK)、蛋白激酶B(AKT)蛋白阳性表达率。Western blotting法检测卵巢癌细胞系HO-8910、HO-8910PM中u PA、P38M APK的表达,观察使用SB203580、U0126、M K-2206分别阻断P38M APK、ERK、AKT信号通路后u PA的变化。结果 u PA、P38MAPK、ERK、AKT在卵巢癌中阳性率分别为61.22%、57.14%、53.06%、55.10%。u PA与卵巢癌病理分期、分化转移有关(P<0.05),且与P38M APK呈正相关(P=0.01),与ERK、AKT表达无关(P>0.05)。ERK、AKT与卵巢癌淋巴结转移、大网膜转移有关(P均<0.05)。HO-8910PM细胞系中u PAt和P38M APK明显高于HO-8910;使用SB203580后u PA表达降低,而使用U0126、M K-2206后u PA无变化。P38M APK、u PA与卵巢癌患者术后生存率呈负相关(Log-rank=3.90,11.04,P=0.048,0)。结论卵巢癌中P38M APK信号通路激活并上调u PA的表达,ERK、AKT信号通路不参与调节u PA表达。P38M APK与u PA在卵巢癌侵袭、转移及评估预后过程中发挥重要作用。

Objective To explore the effects of P38 mitogen-activated protein kinase（ P38 MAPK） signal pathway on the expression of urokinase-type plasminogen activator（ u PA） in ovarian cancer. Methods The expressions of u PA,P38 MAPK,extracellular regulated kinase（ ERK）,and AKT / kinase B in 49 cases of ovarian cancer were detected with immunohistochemistry. The expressions of u PA and P38 MAPK in ovarian cancer cell line HO-8910 and HO-8910 PMwere detected with Western blotting. Changes of u PA were observed after P38 MAPK,ERK and AKT signal pathway were blocked by SB203580,U0126 and MK-2206 respectively. Results The results of immunohistochemistry showed that positive expression rates of u PA,P38 MAPK,ERK and AKT were 61. 22%,57. 14%,53. 06%,and 55. 10%,respectively. The expression of the u PA was related to clinicopathologic stage,differentiation and metastasis（ P〈0. 05）,and positively correlated with P38 MAPK（ P = 0. 01）,but not related to ERK or AKT（ P〈0. 05）. The expressions of AKT and ERK were related to lymph node metastasis and greater omentum metastasis（ P〈0. 05）. The expression of u PA and P38 MAPK in HO-8910 PMwas higher than those in HO-8910,and it reduced when the P38 MAPK signal pathway was blocked by SB203580. But it had no significant change after dealing with U0126 and MK-2206 respectively. The postoperative survival rate was negatively correlated with P38 MAPK and u PA. Conclusion TheP38 MAPK signal pathway are activated in ovarian cancer and it can upregulate the expression of u PA,but ERK and AKT signal pathway are not involved in the regulation of u PA expression,which indicates that P38 MAPK and u PA may play an important role in the invasion,metastasis and prognosis assessment of ovarian cancer.