Association between integrin-linked kinase and hyperthermia in oral squamous cell carcinoma

整合素连接激酶与口腔鳞状细胞癌热疗的关系

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作者:Jun Zhao, Na Liu, Xinhe Hao, Lin Que, Jiyuan Liu, Xiufa Tang

Abstract

The present study aimed to observe the effect of the biological functions of integrin-linked kinase (ILK) silencing combined with hyperthermia on Tca8113 cells. Lentivirus-mediated short hairpin RNA (shRNA)-targeting ILK was transfected into oral squamous cell carcinoma (OSCC) Tca8113 cells and, combined with hyperthermia, several experimental methods were used to detect their biological behavior in vitro. On the basis of in vitro experiments, Tca8113 cells were transplanted into nude mice models, and ILK-shRNA-lentivirus was injected into the nude mice transplanted tumor and combined with hyperthermia. Tumor morphology and the associated protein expression changes were determined. Subsequent to ILK silencing combined with hyperthermia, the growth, migration and proliferation of Tca8113 cells were significantly inhibited. Flow cytometry revealed that the cells were blocked in the S phase, and western blot analysis demonstrated that ILK, phosphorylated (p)-RAC-alpha serine/threonine-protein kinase (Akt), p-glycogen synthase kinase-3β and p-heat shock factor 1 protein expression levels were significantly decreased, while apoptosis-associated protein B-cell lymphoma-2-associated X protein expression and the efficacy of hypothermia were significantly increased. By ILK silencing combined with hyperthermia, a significant therapeutic effect on transplanted tumors was observed in nude mice. Immunohistochemistry revealed the same results as the in vitro experiments. ILK silencing combined with hyperthermia can inhibit the growth, proliferation and migration of Tca8113 cells, promote Tca8113 cell apoptosis, inhibit the phosphatidylinositol-3-kinase/Akt signaling pathway and increase hyperthermia sensitivity; the combination therapy exhibits a synergistic sensitizing effect. Therefore, ILK silencing combined with hypothermia may serve as a novel combination therapy strategy against OSCC.

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