The Effect Of Resveratrol On Acute T Lymphocytic Leukemia In Mice And The Mechanism Of Autophagy

Objective: To explore the effects and its possible mechanism of resveratrol on autophagy in acute T-lymphocytic leukemia(T-ALL)of mouse by observing the expression levels of the autophagy-related proteins Beclin1,P62,LC3-II/I and molecules in the AMPK/m TOR signaling pathway.Methods: 1.Fifteen female C57BL/6 mice aged 6-8 weeks were randomly divided into normal control group(CON),T-ALL model group(T-ALL)and resveratrol(100 mg/kg/d)treatment group(Res).T-ALL group and Res group mice were injected with ICN1-GFR+ T-ALL cells in the tail vein to construct T-ALL leukemia mouse model.2.Flow cytometry(FCM)was used to detect the percentage of GFR+ T-ALL cells in peripheral blood and spleen tissue of each group.3.The pathological morphology changes of spleen tissues were examined by HE staining in mice of each group.4.Real-time fluorescence quantitative PCR(RT-PCR)was used to detect the expression of Beclin1 m RNA in the spleen tissue of mice in each group.5.Western blot was used to detect the changes of autophagy-related proteins(Beclin1,P62,LC3-II/Ⅰ)and AMPK/m TOR pathway-related proteins(p-AMPK/AMPK,p-m TOR/m TOR)in the spleen tissue of each group of mice.Results: 1.Mice in T-ALL group were debilitated,wasted,and had gait instability.Compared with T-ALL group,the mental state and diet activity of mice in Res group were sigificantly improved.2.FCM results showed that the percentage of GFP+ T-ALL cells in the peripheral blood and spleen of mice in Res group was significantly reduced compared with T-ALL group(P <0.05).3.HE results showed that resveratrol significantly inhibited the infiltration of GFR+T-ALL cells into spleen tissue of mice and reducd the destruction of spleen.4.RT-PCR results showed that Beclin1 m RNA expression level in the spleen of Res group mice was significantly higher than in the T-ALL group(P <0.05).5.Western Blot results showed that compared with the T-ALL group,the expression levels of autophagy-related proteins Beclin1,LC3-Ⅱ/ protein in Ⅰthe spleen of Res mice were significantly increased(P <0.05),and the levels of P62 protein were significantly reduced(P<0.05);The expression of p-AMPK/AMPK protein was significantly up-regulated(P<0.05),and p-m TOR/m TOR protein was significantly down-regulated(P<0.05).Conclusions: Resveratrol have an anti-T-ALL effect by enhancing cellular autophagy,which may be related to activating the AMPK/m TOR signaling pathway.