白藜芦醇调控LKB1/AMPK通路对乳腺癌细胞增殖、迁移和糖酵解的研究OA

Objective To explore the effects and mechanism of resveratrol on the proliferation,migration and glycolysis of breast cancer cells by regulating the liver kinase B1(LKB1)/AMP activated protein kinase(AMPK)pathway.Methods Human breast cancer MDA-MB-231 cells were divided into four groups:control group,low-concentration experimental group(25 μmol·L-1 resveratrol),high-concentration experimental group(50 μmol·L-1 resveratrol)and inhibitor group(50 μmol·L-1 resveratrol+4 μmol·L-1 AMPK inhibitor BML-275).The cell proliferation of each group was detected by thiazolyl blue(MTT)assay and Edu staining;the cell migration was detected by scratch test;the cell apoptosis was detected by flow cytometry;the glucose consumption and lactic acid production of cells in each group were measured by glucose content kit and lactic acid content kit,respectively;the protein expressions of glucose transporter 1(GLUT1),lactate dehydrogenase A(LDHA),hexokinase 2(HK2),LKB1 and AMPK in each group were detected by Western blot.Results The cell proliferation inhibition rates of control group,low-concentration experimental group,high-concentration experimental group and inhibitor group were(0±0)％,(32.27±3.68)％,(56.75±5.82)％and(24.41±3.06)％,respectively;the Edu-positive rates were(52.64±6.95)％,(30.72±4.21)％,(18.86±2.54)％and(41.37±4.88)％,respectively;the scratch healing rates were(34.24±3.82)％,(23.67±2.74)％,(14.85±2.03)％and(29.74±3.42)％,respectively;the cell apoptosis rates were(3.04±0.32)％,(21.81±2.64)％,(34.43±3.86)％and(12.67±1.93)％,respectively;the glucose consumption levels were(31.74±3.52),(23.18±2.64),(14.33±1.67)and(28.27±3.12)μmol·L-1,respectively;the lactic acid production levels were(48.12±4.43),(31.27±3.75),(18.85±2.14)and(42.36±4.19)μmol·L-1,respectively;the relative expression levels of GLUT1 were 1.14±0.12,0.76±0.08,0.41±0.04 and 0.94±0.09,respectively;the relative expression levels of LDHA were 1.32±0.14,0.89±0.09,0.47±0.05 and 1.13±0.12,respectively;the relative expression levels of HK2 were 0.97±0.09,0.61±0.06,0.34±0.04 and 0.86±0.09,respectively;the relative expression levels of LKB1 were 0.93±0.10,1.38±0.14,1.75±0.17 and 1.12±0.11,respectively;the relative expression levels of AMPK were 1.02±0.11,1.56±0.16,2.04±0.23 and 1.18±0.13,respectively.Compared with control group,the above indicators in the low-and high-concentration experimental groups were statistically significantly different(all P＜0.05);compared with the high-concentration experimental group,the above indicators in the inhibitor group were statistically significantly different(all P＜0.05).Conclusion Resveratrol may inhibit the proliferation,migration and glycolysis of breast cancer cells by activating the LKB1/AMPK pathway.