黄芩素抑制白血病细胞增殖的分子机制研究

Study on molecular mechanism by which baicalein inhibits leukemic cell proliferation

摘要:

目的探讨黄芩素抑制白血病细胞增殖的分子机制。方法用不同终浓度的黄芩素处理多种白血病细胞，通过细胞计数获得不同时间的活细胞数，绘制细胞的生长曲线。采用对黄芩素处理最敏感的6133/MPLW515L细胞，探讨黄芩素抑制白血病细胞增殖的分子机制、细胞周期分布及凋亡情况。结果黄芩素能抑制实验中所有白血病细胞的增殖，但对来自小鼠胚胎干细胞非恶变的G1ME 细胞却无效果，提示黄芩素可能特异性抑制恶变白血病细胞增殖。细胞周期分析显示，不同浓度的黄芩素对6133/MPL W515L 细胞凋亡的作用不同（p <0.05），提示可能导致6133/MPL W515L细胞凋亡和将细胞周期阻滞于G1期。另外，黄芩素可能通过抑制MAPK/Erk 通路，激活Caspase-3 的方式诱导细胞凋亡。单独Z-VAD 不影响细胞增殖，但也不能拯救黄芩素导致的细胞增殖抑制，提示Caspase 活化可能不是黄芩素抑制细胞增殖的关键通路。结论黄芩素能诱导白血病细胞凋亡和细胞周期阻滞，从而抑制其增殖，可能是有效的抗白血病候选药物。

Abstract:

Objective To investigate the molecular mechanism of baicalein inhibiting proliferation of leukemic cells. Methods A variety of leukemia cells were treated with different concentrations of baicalein, and the number of viable cells was obtained by cell counting. 6133/MPL W515L cells were used to study the molecular mechanism of baicalein inhibition of cell proliferation, cell cycle distribution and apoptosis. Results Baicalein could inhibit the proliferation of all the tested leukemia cells, except for the non malignant G1ME cells from mouse embryonic stem cells, suggesting that baicalein might specifically inhibit the proliferation of malignant leukemia cells. Cell cycle analysis showed that the different concentrations of baicalein had different effect on apoptosis of 6133/MPL W515L cells (p < 0.05), suggesting that may lead to the apoptosis of 6133/MPL W515L cells and cell cycle arrest in G1 phase. In addition, baicalein may induce apoptosis by inhibiting MAPK/Erk pathway and activating caspase-3. Z-VAD alone did not affect cell proliferation, but it could not save the cell proliferation inhibition induced by baicalein, suggesting that caspase activation may not be the key pathway of baicalein inhibiting cell proliferation. Conclusions Baicalein can induce apoptosis and cell cycle arrest and inhibit the proliferation of leukemia cells. It may be an effective candidate for anti-leukemia drugs.