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HO-1 的高表达预示着卵巢癌患者预后不良,并促进卵巢癌细胞的增殖和侵袭。

High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

出版信息

Clin Transl Oncol. 2018 Apr;20(4):491-499. doi: 10.1007/s12094-017-1738-7. Epub 2017 Aug 14.

Abstract

PURPOSE

HO-1 has been proved to be associated with tumor aggressivity and poor prognosis in various cancers. Our study provides the first study to demonstrate the relationship of HO-1 expression and clinical characteristics in ovarian cancer patients.

METHODS

Immunohistochemistry and western blotting were used to examine the expression of HO-1 in tissue species and fresh tissues. CCK-8 was used to investigate cell viability. Transwell chamber was performed to estimate migration and invasion capacities in A2780 and Skov-3 cells.

RESULTS

Immunohistochemistry and western blotting showed that the expression of HO-1 was higher in ovarian cancer tissues than normal ovarian tissues. High expression of HO-1 was significantly associated with serous ovarian cancer, high FIGO stage, lymph node metastasis, and non-optimal debulking. Patients with high expression of HO-1 exhibited an unfavorable prognosis. In vitro inducing the expression of HO-1 promoted the proliferation and metastasis of A2780 and Skov-3 cells, with the increased expressions of mesenchymal marker (Vimentin), epithelial-mesenchymal transition-associated transcript factor (Zeb-1), anti-apoptotic protein (Bcl-2), and the decreased expressions of epithelial marker (Keratin) and pro-apoptotic protein (Bax). Meanwhile, after incubating A2780 and Skov-3 together with HO-1 inhibitor, above results could be reversed.

CONCLUSION

HO-1 might be a potential marker for prediction of ovarian cancer prognosis and a target for ovarian cancer treatment.

摘要

目的

HO-1 已被证明与多种癌症的肿瘤侵袭性和不良预后相关。本研究首次证明了 HO-1 表达与卵巢癌患者临床特征的关系。

方法

免疫组织化学和 Western blot 用于检测组织标本和新鲜组织中 HO-1 的表达。CCK-8 用于研究 A2780 和 Skov-3 细胞的活力。Transwell 室用于评估迁移和侵袭能力。

结果

免疫组织化学和 Western blot 显示,HO-1 在卵巢癌组织中的表达高于正常卵巢组织。HO-1 的高表达与浆液性卵巢癌、FIGO 高分期、淋巴结转移和非最佳减瘤术显著相关。HO-1 高表达的患者预后不良。体外诱导 HO-1 的表达促进了 A2780 和 Skov-3 细胞的增殖和转移,间充质标志物(波形蛋白)、上皮间质转化相关转录因子(Zeb-1)、抗凋亡蛋白(Bcl-2)的表达增加,而上皮标志物(角蛋白)和促凋亡蛋白(Bax)的表达减少。同时,在用 HO-1 抑制剂孵育 A2780 和 Skov-3 后,上述结果可以逆转。

结论

HO-1 可能是预测卵巢癌预后的潜在标志物,也是卵巢癌治疗的靶点。

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