葡萄糖调节蛋白78在卵巢癌侵袭转移中的作用

Role of glucose-regulated protein 78 in the invasion and metastasis of ovarian cancer

目的:探讨葡萄糖调节蛋白78(GRP78)在卵巢癌侵袭转移中的作用。方法:免疫组织化学法检测60例卵巢浆液性癌和40例卵巢浆液性囊腺瘤组织中GRP78的表达情况,Western blotting法检测GRP78的表达水平,分析GRP78的表达与卵巢浆液性癌临床病理指标之间的关系。采用Transwell小室法检测HO-8910细胞和HO-8910PM细胞侵袭、迁移能力;分别使用shRNA-GRP78干扰和pcDNA-GRP78过表达GRP78检测HO-8910PM细胞和HO-8910细胞侵袭、迁移能力的变化。结果:免疫组织化学结果显示,GRP78在卵巢浆液性癌组织中的阳性表达率为90%,明显高于卵巢浆液性囊腺瘤的25%(P<0.01)。GRP78在卵巢浆液性癌组织中表达水平高于卵巢浆液性囊腺瘤组织。GRP78表达水平高的卵巢浆液性癌病人,临床病理分级、分期更高,糖类抗原125水平更高,且发生淋巴结转移、盆腔转移、盆腔外转移的病人比例更高(P<0.01)。体外研究结果显示,GRP78在高转移潜能的HO-8910PM细胞中的表达明显高于低转移潜能的HO-8910细胞(P<0.01)。在HO-8910细胞中过表达GRP78可明显促进细胞的侵袭、迁移能力,而在HO-8910PM细胞中干扰GRP78的表达可明显降低细胞的侵袭、迁移潜能(P<0.01)。结论:卵巢癌组织中GRP78可促进卵巢癌细胞的侵袭、迁移能力。

Objective:To investigate the role of glucose-regulated protein 78(GRP78) in the invasion and metastasis of ovarian cancer. Methods:The expression levels of GRP78 in 60 ovarian serous carcinoma and 40 ovarian serous cystadenoma tissues were detected using the immunohistochemistry(IHC) and Western blotting.The relationship between the clinical indicators of ovarian serous carcinoma and GRP78 expression was analyzed.The invasion and migration ability of HO-8910 cells and HO-8910PM cells were detected using Transwell assay.The invasion and migration ability of HO-8910 cells and HO-8910PM cells treated with shRNA-GRP78 interference and pcDNA-GRP78 overexpression were detected,respectively. Results:The results of IHC showed that the positive expression rate of GRP78 in ovarian serous carcinoma tissues(90%) was significantly higher than that in ovarian serous cystadenoma tissues(25%)( P <0.01).The results of Western blot showed that the expression level of GRP78 in ovarian serous carcinoma tissue was significantly higher than that in ovarian serous cystadenoma tissue.Among the ovarian serous carcinoma patients with high GRP78 expression level,the clinicopathological grade and stage and carbohydrate antigen 125 level were higher,and the proportion of patients with lymph node metastasis,pelvic metastasis,and external pelvic metastasis was higher( P <0.01).The results of in vitro studies showed that the expression level of GRP78 in HO-8910PM cells with high metastatic potential was significantly higher than that in HO-8910 cells with low metastatic potential( P <0.01).The overexpression of GRP78 in HO-8910 cells could promote the invasion and migration ability of the cells,while silencing GRP78 expression in HO-8910PM cells could significantly reduce the invasion and migration potential of the cells( P <0.01). Conclusions:GRP78 can promote the invasion and migration potential of ovarian cancer cells.