Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Clin Transl Oncol. 2018 Apr;20(4):491-499. doi: 10.1007/s12094-017-1738-7. Epub 2017 Aug 14.
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.
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.
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.
HO-1 might be a potential marker for prediction of ovarian cancer prognosis and a target for ovarian cancer treatment.
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。
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。
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。
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。