NOX4对高糖代谢乳腺癌细胞侵袭转移能力的作用

Effect of NOX 4 on the Invasion and Metastasis of Breast Cancer Cells with High Glucose Metabolism

利用2-氟[18F-2]脱氧葡萄糖([18 F]fluorodeoxyglucose,18F-FDG)乳腺癌细胞摄取实验筛选高糖酵解率的乳腺癌细胞;采用基因沉默技术,降低细胞烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX 4)表达;采用免疫印迹方法检测三组细胞(空白对照组、非特异性siRNA转染组和特异性NOX 4-siRNA转染组)的上皮间质转化(epithelial mesenchymal transition,EMT)相关分子HIF-1α和TGF-β表达水平;通过细胞侵袭实验分析三组细胞的侵袭能力差异。结果显示,高侵袭力的MDA-MB-231较低侵袭力的MCF-7乳腺癌细胞系具有高糖酵解率(t=10.52,P<0.05);抑制MDA-MB-231细胞的NOX 4表达,降低了细胞EMT相关因子HIF-1α、TGF-β表达(P均<0.01)与细胞侵袭能力(t=-8.0,P<0.01)。本研究初步证实NOX 4失活能够降低高糖代谢乳腺癌细胞的侵袭转移能力。

The breast cancer cells with high glucose metabolism were screened by ^18F- FDG cell uptake experiment. The gene silencing technique was used to reduce NOX 4 expression in cells. The experiment was divided into three groups： control group, the non-specific transfection group and specific transfection group. Western blotting was used to detect differences in the expression of HIF-1α and TGF-β in three groups. The invasion ability of the three groups by transwell cell invasion assay was analyzed. The results showed that MDA-MB-231 breast cancer ceils had a higher rate of glycolysis than MCF-7 tumor cells（t=10.52, P〈0.05）. The expression of HIF-1α and TGF-β and the invasiveness of cells were reduced by inhibiting the level of NOX 4. This study showed that inhibition of NOX 4 expression was able to inhibit the invasion of breast cancer cell with high glucose metabolism.