目的探讨汉黄芩素对肝癌细胞HepG2的生长抑制和诱导凋亡作用，并研究其作用的机制。方法应用四甲基偶氮唑蓝比色法，测定汉黄芩素对HepG2细胞株活性的影响，检测其抑制肝癌细胞的剂量效应;应用形态学观察、HE染色、4′，6-二脒基-2-苯基吲哚(DAPI)荧光检测和AnnexinV-PI流式检测，评价汉黄芩素对HepG2细胞的凋亡作用，并进行细胞周期的分析，蛋白质印迹法检测组蛋白去乙酰化酶1和组蛋白去乙酰化酶2蛋白表达情况。结果汉黄芩素对HepG2细胞具有生长抑制及诱导凋亡作用，且呈剂量依赖性;并观察到细胞出现核变形、染色体凝集，出现明显的凋亡峰，细胞周期阻滞在G2/M期，蛋白质印迹法结果显示，组蛋白去乙酰化酶1和组蛋白去乙酰化酶2表达量未变化，多聚(ADP-核糖)聚合酶降解产物增加。结论汉黄芩素对肝癌HepG2细胞的增殖有抑制作用，通过阻滞细胞周期促进细胞凋亡。
Abstract
OBJECTIVE To study the growth inhibitory and apoptosis-inducing effect of wogonin on hepatocarcinoma cell line HepG2. METHODS HepG2 cell line was treated with various concentrations of wogonin. Proliferation was determined by MTT test and morphology observation.Flow cytometry was applied to detect the wogonin-induced apoptosis and to analyse the cell cycle. Western blot was used to detect HDAC1 and HDAC2 expression. RESULTS Wogonin had a growth inhibitory and apoptosis-inducing effect on HepG2 cell. The cell showed G2/M arrest by cell cycle analysis. A characteristic apoptosis change including nuclear disintergration and chromatin agglomerate was displayed. Western blot results show increase of cleave PARP, but not change in HDAC1, HDAC2 expression. CONCLUSION Wogonin has a growth inhibitory and apoptosis-inducing effect on hepatocarcinoma cell line HepG2.
关键词
汉黄芩素 /
HepG2 /
凋亡 /
肝癌 /
抗肿瘤
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Key words
wogonin /
HepG2 /
apoptosis /
hepatoma /
anti-tumor
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中图分类号：
R965
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参考文献
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LI D R, ZHANG H Y,ZHANG W, et al . The inhibitory role of wogonin on tumor growth and telomerase activity of human ovarian cancer SKOV3 cell line xenograf in nude mice.Chin Pharmacol Bull(中国药理学通报), 2007,23(4):534-538.
LU X,WU X L,LI Y, et al. Inhibitory effect of wogonin on gastric cancer SGC7901 cell line in vitro.Chin Pharm J(中国药学杂志), 2011,46(7):512-517.
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MILLER K,TJEERTES J V, COATES J, et al . Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining.Nat Struct Mol Biol,2010,17(9): 1144-1151.
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BOULARES A H, YAKOVLEV A G, IVANOVA V, et al . Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem, 1999,274(33):22932-22940.
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脚注
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基金
黔科合计省合7006号;2011“西部之光”人才项目;省长专项74;广州医学院博士科研项目(2012C16)
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