二氢杨梅素通过STAT3/Bcl-2信号通路促进HNSCC细胞自噬和凋亡

Dihydromyricetin promotes autophagy and apoptosis in head and neck squamous cell carcinoma cells through STAT3/Bcl-2 signaling pathway

目的:探讨二氢杨梅素(DHM)对人头颈鳞癌(HNSCC)细胞增殖及凋亡的影响。方法:分别用不同浓度(12.5、25、50 μmol/L)DHM处理人HNSCC SCC-25细胞6、12、24 h,用流式细胞仪检测SCC-25细胞凋亡情况;用细胞免疫荧光法观察SCC-25细胞中自噬小体产生情况;Western印迹法检测SCC-25凋亡和自噬标志物的表达。结果:12.5、25、50 μmol/L的DHM处理24 h后,SCC-25细胞凋亡逐渐增加;细胞中凋亡标志物CL-PARP、Bax、CL-casp3逐渐增加,Bcl-2逐渐减少(P<0.05)。12.5、25、50μmol/L的DHM处理24 h后,SCC-25细胞自噬逐渐增强;自噬标志指标p-STAT3表达上调,LC3Ⅱ/LC3Ⅰ的比值逐渐加大,Beclin 1增加,p62逐渐减少(P<0.05)。抑制自噬能促进DHM诱导的SCC-25细胞凋亡,细胞凋亡标志物CL-PARP、Bax增加,Bcl-2减少(P<0.05)。结论:DHM能诱导HNSCC细胞凋亡及自噬,其机制与STAT3相关信号通路有关;抑制自噬能促进DHM诱导的HNSCC细胞凋亡。

Objective：To study the effects of dihydromyricetin（DHM）on cell proliferation and apoptosis of head and neck squamous cell carcinoma（HNSCC）.Methods：SCC-25 cancer cells were treated with 12.5,25,50 μmol/L DHM for 6,12,and 24 h.SCC-25 cell apoptosis was detected by flow cytometry.Immunofluorescence was used to observe the emergence of autophagosomes in HNSCC cells.Western blotting was used to detect the expression of apoptosis and autophagy markers in SCC-25.Results：After treatment of 12.5,25,and 50 μmol/L DHM for 24 h,the apoptosis of SCC-25 cells gradually increased;the apoptotic markers CL-PARP,Bax,and CL-casp 3 gradually increased and Bcl-2 gradually decreased（P〈0.05）.After treatment of 12.5,25,and 50 μmol/L DHM for 24 h,in line with the apoptosis,the autophagy markers of SCC-25 cells gradually changed,the p-STAT3 expression was up-regulated;the ratio of LC3 Ⅱ/LC3 Ⅰ gradually increased,Beclin 1 increased,p62 gradually decreased（P〈0.05）.Inhibition of autophagy could promote apoptosis of SCC-25 cells which were induced by DHM,increase apoptosis markers CL-PARP and Bax,and decrease Bcl-2 （P〈0.05）.Conclusions：DHM can induce apoptosis and increase autophagy of HNSCC cells.The mechanism is related to STAT3 signaling pathway.Inhibition of autophagy can promote apoptosis of HNSCC cells induced by DHM.