OBJECTIVE To investigate inhibitory effect of dicentrine on human lung cancer cell line A549 and its mechanism. METHODS Growth inhibition of dicentrine 0 - 200 μmol·L-1 on human lung cancer cell line A549 was examined by MTT colorimetric assay. Inhibitory effect of dicentrine 0-20 mol·L -1 on telomerase was examined by telomerase repeat amplification protocol (TRAP). Moreover, the anti-tumor mechanism of dicentrine 9μmol·L-1 was explored by using UV-vis spectra experiment to examine G-quadruplex stability. RESULTS The inhibitory effect of the dicentrine on A549 cells increased in a concentration- (r =0.906) and time-dependent (r =0.949) manner(P<0.05) , tumor inhibitory rates of dicentrine 25, 50, 100, 200 (xmol·L-1 on A549 tumor were 33.4% , 88.2% , 88.6% and 89. 4% at 72 h, respectively. Dicentrine could significantly decreased telomerase activity (P<0.05); from results of G-quadruplex stability experiments, the quadruplex structure showed increasing Tm values with dicentrine, value of Tm from 48℃ up to 54×1. CONCLUSION Dicentrine can significantly decrease telomerase activity by stabilizing G-quadruplex structure. Accordingly, it can significantly inhibit the proliferation of A549 cells.%目的 探讨荷包牡丹碱对人肺癌A549细胞生长的抑制作用及其作用机制.方法 A549细胞加入荷包牡丹碱0～200 μmol·L -分别作用24,48和72 h,MTT法测定A549细胞的生长抑制作用.荷包牡丹碱0 ～ 20 μmol·L-1作用72 h,端粒重复序列扩增(TRAP)法测定端粒酶活性.变温紫外法检测荷包牡丹碱9 μmol· L-1对端粒酶G-四链体的稳定作用.结果 荷包牡丹碱25,50,100和200 μmol·L-1作用细胞72 h后的抑制率分别为33.4％,88.2％,88.6％和89.4％,明显高于正常对照组细胞(P＜0.05),并具有量效(r =0.906,P＜0.05)和时效(r=0.949,P＜0.05)性.与正常对照组相比,荷包牡丹碱5,10,15和25μmol·L-1可有效抑制A549细胞端粒酶的活性(P＜0.05),相对TRAP端粒酶活性从正常对照组的1.471±0.102分别降低为1.093±0.054,1.013±0.016,0.554±0.034,0.365±0.081 (P ＜0.05).荷包牡丹碱9μmol·L -使G-四链体的熔点值从正常对照组的48℃提高到54℃.结论 荷包牡丹碱可以通过稳定G-四链体结构,抑制端粒酶活性,有效抑制人肺腺癌细胞A549的生长.
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