Abstract
Objective To investigate the mechanism of the radiosensitivity effect of Cox-2 gene in esophageal cancer. Methods Cox-2 specific siRNA was constructed and transfected to EC9706 cells to downregulate intracellular Cox-2 expression. The expressions of MMP-2, Bcl-2 mRNA, AKT and phosphorylated AKT proteins were assayed after radiation. Colony formation, cell proliferation, apoptosis and cell invasion in vitro were examined as well. One-way ANOVA method was used to analyze the data. Results After 2 and 4 Gy irradiation, a significant increase in the mRNA expression of Bcl-2 was observed in the Cox-2 up-regulation group(F=3.36, 4.32, P<0.05). In the group of Cox-2 downregulation, the expression of MMP-2 mRNA was significantly reduced(F=3.86, 8.09, P<0.05). After irradiation, a significant decrease of Bcl-2 mRNA(F=3.73, 5.64, P<0.05) as well as an increase of Bax(F=7.03, 7.42, P<0.05)was detected, and the levels of total and phosphorylated AKT proteins had the highest level in the Cox-2 upregulation group and had the lowest level in the Cox-2 downregulation group. In the Cox-2 downregulation group, the apoptosis induction obviously increased with dose(F=317.40, P<0.05), and the proportion of cells in G0-G1 phase gradually increased but the proportion of cells in S and G2-M phases decreased, concomitant with the obvious suppression of cell proliferation, in addition, cell invasion was decreased. Conclusions Downregulation of intracellular Cox-2 mRNA expression, concomitant with subsequent downregulation of MMP-2 and Bcl-2 and upregulation of Bax, resulted in reduction of the invasion and metastatic capabilities of tumor cells, and induction of G0-G1 phase arrest and apoptosis. Downregulation of AKT and phosphorylated AKT (pAKT) protein expression might also interfere with the capability of the PI3K/Akt signal transduction pathway to resist radiotherapy. Key words: Cox-2 gene; Esophageal cancer; Radiosensitivity; Mechanism
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