氧化苦参碱及苦参碱Au(Ⅲ)金属配合物对肿瘤细胞增殖的影响及分子机制初探

Effect of Au(Ⅲ) complex with oxymatrine and matrine on proliferation of tumor cells in vitro and its mechanisms

目的合成氧化苦参碱Au(Ⅲ)金属配合物(OMT-Au)和苦参碱Au(Ⅲ)金属配合物(MT-Au),并比较2种配合物体外抑制肿瘤细胞增殖的效果,初步探讨其分子机制及构效关系。方法溶剂热法合成配合物,X射线单晶衍射表征结构,不同剂量配合物分别处理10种肿瘤细胞株,MTT法观察细胞增殖抑制,流式细胞术检测配合物对细胞凋亡和细胞周期的影响,琼脂凝胶电泳探究配合物对拓扑异构酶Ⅰ(TOPO Ⅰ)活性的影响。结果 OMT-Au明显抑制人胃癌MGC803细胞增殖,阻滞MGC803细胞于G2/M期,抑制TOPOI介导的p UC19DNA质粒的解旋反应,呈剂量依赖关系,且抑制作用均强于MT-Au配合物。结论 OMT-Au抗肿瘤活性强于MT-Au,原因可能与配体的分子构象差异有关。

Objective To synthesize metal complexes of Au(Ⅲ) with matrine(MT-Au) and oxymatrine(OMT-Au), compare their inhibitory effect on the proliferation of tumor cells in vitro, and discuss the mechanism and structure-activity relationship. Methods The metal complexes were synthesized by solvothermal method and characterized by X-ray single crystal diffraction. The in vitro cytotoxicity of complexes with different doses towards 10 selected tumor cell lines was evaluated by MTT method. The effects of complex on cell apoptosis and cell cycle were investigated by flow cytometer. Agarose gel electrophoresis was used to study the effects of complex on topoisomerase I(TOPO Ⅰ) activity. Results Complex OMT-Au obviously inhibited the proliferation of MGC803 tumor cells, blocked cell cycle of MGC803 in G2/M phase, and suppressed TOPO Ⅰ mediated untwisting of pUC19 DNA plasmid with a dose-dependence manner. And the inhibited effects of complex OMT-Au were all stronger than MT-Au complex. Conclusion The antitumor activity of complex OMT-Au is stronger than that of MT-Au, which could be attributed to the variation in the molecular conformation of ligand.