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鸟嘌呤富集序列可形成稳定的一种核酸二级结构,G-四链体,其广泛存在于基因组中.稳定G-四链体的化学小分子可以抑制肿瘤细胞增长,然而,G-四链体作为药物靶标的可行性还有待证实.在本研究中,我们发现靶向酪氨酸激酶治疗肿瘤的药物舒尼替尼,稳定端粒G-四链体结构.舒尼替尼与异喹啉类生物碱小檗碱的组合使用增强舒尼替尼对端粒G-四链体稳定.圆二色谱实验证明,这种的协同效应可能是由于两种药物的组合诱导了端粒末端G-四链体的构型转变.30 μM小檗碱与6 μM舒尼替尼联用之后,细胞凋亡率达到70％,与单独使用6μM舒尼替尼的效果相比,提高了1.7倍.荧光共聚焦显微实验表明,舒尼替尼和小檗碱联用增加人体腺癌细胞端粒末端G-四链体的形成.本研究预示很多的临床药物可能通过靶向端粒G-四链体而起作用.“,”G-quadruplexes are stable secondary structures formed with guanine rich sequences,which are widely distributed in genome.Chemical compounds stabilizing G-quadruplexes exhibited inhibition on tumor cells.However,the feasibility of G-quadruplex structures as drug targets needs to be validated.In this study,Sunitinib,an antitumor drug targeting tyrosine kinases was found to stabilize telomere G-quadruplex.The stabilization was further enhanced by the combined usage with Berberine,an isoquinoline alkaloid.Circular dichroism spectra showed the synergistic effect comes from inducing the conformation conversion of telomere G-quadruplex.The combination of Berberine with Sunitinib resulted in 1.7-fold enhancement in cell apoptosis rate with the percentage of apoptotic cells reaching about 70％.The confocal microscopy immunofluorescence images showed the combination of Berberine and Sunitinib induced the formation of G-quadruplex at the telomere in A549 cancer cells.This study suggested that more clinic drugs could work by targeting G-quadruplex structures.