钌配合物[Ru(MeIm)_4(dpq)]^(2+)与G-四链体DNA的相互作用及抗肿瘤活性

Interaction between ruthenium complex [Ru(MeIm)_4(dpq)]^(2+) and G-quadruplex DNA and the antitumor activity of ruthenium complex

目的研究钌配合物[Ru(Me Im)4(dpq)]与端粒DNA:HTG21(AG3(T2AG3)3)的相互作用,并初步探讨其体外抗肿瘤活性。方法应用紫外-可见吸收光谱、圆二色谱、荧光共振能量转移和显色反应实验研究钌配合物与HTG21的相互作用;采用MTT法检测其对肿瘤细胞株A549、He La、Hep G2细胞增殖的影响,用流式细胞术、Hoechst33342荧光染色检测细胞周期及细胞凋亡的变化。结果钌配合物与G-四链体之间存在较强亲和力,可诱导人体端粒HTG21形成G-四链体并稳定该结构,阻滞A549细胞在S期并诱导肿瘤细胞凋亡。结论钌配合物可能通过稳定端粒DNA发挥抗肿瘤活性,端粒DNA可能是钌配合物抗肿瘤作用的靶点。

Objective To study the interaction between ruthenium complex [Ru（Me Im）4（dpq）] and telomere DNA sequences HTG21（AG3（T2AG3）3） and the antitumor activity of ruthenium complex. Methods Ultraviolet and visible spectroscopy, circular dichroism spectroscopy, fluorescence resonance energy transfer and color reaction were used to detect the interaction between [Ru（Me Im）4（dpq）]2＋ and HTG21. Their effects on proliferation, cell cycle and apoptosis of human cancer cell lines including A549, He La and Hep G2 were determined using MTT assay, flow cytometry, and Hoechst33342 staining, respectively. Results The ruthenium complex was tightly bound to the G-quadruplex DNA, and induced HTG21 to form the stable Gquadruplex. The ruthenium complex induced the cell cycle arrest in S phase and apoptosis of A549 cells. Conclusion The ruthenium complex may possess an antitumor activity by stabilizing telomere DNA. The telomere DNA might be the anti-tumor target for the ruthenium complex.