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

doi:10.6040/j.issn.1671-7554.0.2015.081

摘要/Abstract

摘要： 目的探讨卵巢癌细胞及组织中分子量为38 kD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(uPA)的影响。方法应用免疫组化SP法检测49例卵巢癌组织中uPA、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uPA、P38MAPK的表达,观察使用SB203580、U0126、MK-2206 分别阻断P38MAPK、ERK、AKT信号通路后uPA的变化。结果 uPA、P38MAPK、ERK、AKT在卵巢癌中阳性率分别为61.22%、57.14%、53.06%、55.10%。uPA与卵巢癌病理分期、分化转移有关(P<0.05),且与P38MAPK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uPAt和P38MAPK明显高于HO-8910;使用SB203580后uPA表达降低,而使用U0126、MK-2206后uPA无变化。P38MAPK、uPA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P38MAPK信号通路激活并上调uPA的表达,ERK、AKT信号通路不参与调节uPA表达。P38MAPK与uPA在卵巢癌侵袭、转移及评估预后过程中发挥重要作用。

关键词: 尿激酶型纤维蛋白酶原激活剂, P38MAPK信号通路, 卵巢肿瘤, 细胞外调节蛋白激酶, 蛋白激酶B

Abstract: Objective To explore the effects of P38 mitogen-activated protein kinase(P38MAPK)signal pathway on the expression of urokinase-type plasminogen activator(uPA)in ovarian cancer. Methods The expressions of uPA, P38MAPK, extracellular regulated kinase(ERK), and AKT/kinase B in 49 cases of ovarian cancer were detected with immunohistochemistry. The expressions of uPA and P38MAPK in ovarian cancer cell line HO-8910 and HO-8910PM were detected with Western blotting. Changes of uPA were observed after P38MAPK, 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 uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06%, and 55.10%, respectively. The expression of the uPA was related to clinicopathologic stage, differentiation and metastasis(P<0.05), and positively correlated with P38MAPK(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 uPA and P38MAPK in HO-8910PM was higher than those in HO-8910, and it reduced when the P38MAPK 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 P38MAPK and uPA. Conclusion The 山东大学学报 (医学版)54卷2期 -张春霞,等.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 \=-P38MAPK signal pathway are activated in ovarian cancer and it can upregulate the expression of uPA, but ERK and AKT signal pathway are not involved in the regulation of uPA expression, which indicates that P38MAPK and uPA may play an important role in the invasion, metastasis and prognosis assessment of ovarian cancer.

Key words: Ovarian tumor, Urokinase-type plasminogen activator, P38MAPK signal pathway, Extracellular regulated protein kinases, Protein kinase B

中图分类号:

R737.31

张春霞,邹存华,宋冬冬,余江. 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[J]. 山东大学学报（医学版）, 2016, 54(2): 68-74.

ZHANG Chunxia, ZOU Cunhua, SONG Dongdong, YU Jiang. Effects of P38 mitogen-activated protein kinase signal pathway on the expression of urokinase-type plasminogen activator in ovarian cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 68-74.

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