Preliminary study on the correlation between regulation of Cox-2 gene expression and radiosensitivity of esophageal cancer / 中华放射医学与防护杂志

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 Affter 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).Affter irradiation,a significant decreaseof 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 Go-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 Go-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.