Zeng Yue-Can, Sun Dan, Li Wen-Hui, Zhao Jing, Xin Yan
The Fourth Laboratory of Cancer Institute, Department of Tumor Pathology of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang, China.
Tumour Biol. 2017 Jun;39(6):1010428317704820. doi: 10.1177/1010428317704820.
Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in gastric cancer is not clear. In this study, we evaluated the function and mechanism of gankyrin in gastric cancer. The effects of gankyrin on gastric cancer growth, proliferation, and chemosensitivity were determined. Gankyrin expression was significantly increased in gastric cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin D1, cyclin E, proliferating cell nuclear antigen, phosphoinositide 3-kinase, AKT, p-PI3K, and p-AKT but upregulated Rb, p53, and p27. However, gankyrin overexpression led to opposite results. Downregulation of gankyrin expression enhanced chemosensitivity to 5-fluorouracil and cisplatin by inducing cell apoptosis. However, upregulation of gankyrin expression led to the opposite outcomes. Gankyrin enhanced gastric cancer cell proliferation by regulating cell cycle-related proteins and by activating PI3K/AKT signaling pathway. Gankyrin played an important role in gastric carcinogenesis and could be a potential effective therapeutic target for enhancing chemosensitivity to 5-fluorouracil and cisplatin.
尽管甘菊环蛋白参与了某些恶性肿瘤的致瘤性和转移过程，但它在胃癌中的作用尚不清楚。在本研究中，我们评估了甘菊环蛋白在胃癌中的功能和机制。确定了甘菊环蛋白对胃癌生长、增殖和化疗敏感性的影响。与非癌组织相比，胃癌中甘菊环蛋白的表达显著增加。这种表达在体外和体内均显著增强了癌细胞的增殖和生长。抑制甘菊环蛋白可下调细胞周期蛋白D1、细胞周期蛋白E、增殖细胞核抗原、磷脂酰肌醇3激酶、AKT、p-PI3K和p-AKT，但上调Rb、p53和p27。然而，甘菊环蛋白过表达导致相反的结果。下调甘菊环蛋白表达通过诱导细胞凋亡增强了对5-氟尿嘧啶和顺铂的化疗敏感性。然而，上调甘菊环蛋白表达导致相反的结果。甘菊环蛋白通过调节细胞周期相关蛋白和激活PI3K/AKT信号通路增强胃癌细胞增殖。甘菊环蛋白在胃癌发生过程中起重要作用，可能是增强对5-氟尿嘧啶和顺铂化疗敏感性的潜在有效治疗靶点。
