青蒿琥酯联合热疗对肺腺癌细胞A549增殖和凋亡的影响

Effect of proliferation and apoptosis of artesunate combined thermotherapy on human lung adenocarcinoma A549 cell line

目的观察青蒿琥酯联合热疗对肺腺癌细胞A549的增殖抑制作用。方法将A549分为四组:A组给予不同浓度的青蒿琥酯;B组给予热疗(43℃加热1 h);C组给予青蒿琥酯联合热疗;D组为正常培养A549(对照组)。分别在处理24、48 h时用MTT法检测四组A549的生长抑制情况;流式细胞术检测细胞周期和凋亡率。结果青蒿琥酯对A549生长抑制作用与剂量—效应—时间呈正相关系,在100～800μmol/L的范围内呈线性关系。青蒿琥酯及青蒿琥酯联合热疗作用24 h半数抑制浓度(IC_(50))分别为396μmol/L和172μmol/L。与D组相比,A、C组G_0/G_1期细胞数增多,S期和G_2/M期细胞数减少(P<0.01)。A、C组细胞凋亡率分别为16.77%和28.90%,均高于D组的2.08%(P<0.01)。结论青蒿琥酯、青蒿琥酯联合热疗可抑制A549生长,诱导细胞凋亡可能是其作用机制之一。

Objective To observe the proliferation inhibition of human lung adenocarcinoma A549 cell line treated by artesunate combined thermotherapy. Methods A549 cell line were divided into 4 groups ： A549 were cultured with different artesunate in group A. Hyperthermia at 43 ℃ for 1 h were given to group B. A549 were treated with artesunate combination with hyperthermia in group C, while normally cultured A549 were as control （group D）. Cell growth inhibition ratio were examined with MTT assay after 24 and 48 h respectively. Cell cycle and the apoptosis rate were measured by flow cytometry （FCM）. Results Proliferation of artesunate on A549 were positive correlation with dosage-times effect. There was a linear correlation in the range of 100 - 800 μmol/L artesunate. IC50 of artesunate, artesunate combined thermotherapy in 24 h were 396 μmol/L and 172 μmol/L, respectively. Comparing with group D, number of cell in stage G0/G1 increased and decreased in stage S and G2/M in group A and C（ P 〈0.01 ）. Apoptosis rate of A549 were 28.90% in group A and 16.77% in group C, and were higher than 2.08% in group D（ P 〈 0.01 ）. Conclusions artesunate, artesunate combined thermotherapy have the effect of proliferation inhibition on A549. Inducing apoptosis may be one of its mechanisms.