OBJECTlVE To investigate the correIation between baicaIin metaI(Ni2+,Co2+,Cu2+) compIexes(BmC)with their anti-tumor activity and the abiIity of BmC to bind to hepatoma ceII DNA. METHODS The cheIating Iigand method was used to synthesize BmC,and the composition and struc-ture of BmC were characterized. mTT,PI staining method and AnnexinⅤ-FITC doubIe staining method were used to anaIyze the effect of BmC on SmmC-7721 ceII proIiferation,cycIe and apoptosis,and to expIore their cytotoxic effect on SmmC-7721 ceIIs in combination with morphoIogy. With DNA extracted from hepatoma ceIIs as a target,cycIic voItammetry and AC impedance were used to study the interaction of BmC with DNA. The interaction mechanism between BmC and DNA was expIored. RESULTS Three new types of BmS were successfuIIy prepared. The moIecuIar formuIas of compIexes were Na2 Ni(C21 H16 O11 )2·10H2 O,Na2 Co(C21 H16 O11 )2·8H2 O,and Na2 Cu(C21 H16 O11 )2·8H2 O,respec-tiveIy. CeII proIiferation and morphoIogy detection reveaIed that BmC 6.25-100 mg·L-1 treatment for 24, 48 and 72 h couId inhibit SmmC-7721 ceII survivaI. BmC cytotoxicity was Iisted as foIIows:baicaIin-cop-per( BC-Cu)﹥ baicaIin-cobaIt( BC-Co)﹥ baicaIin-nickeI( BC-Ni)﹥ baicaIin( BC),in a concentration-dependent manner(P﹤0.01)and time-dependent manner(P﹤0.01). According to the resuIts of ceII cycIe and apoptosis detection,BmC retarded the growth of ceIIs from G0 / G1 phase into S phase or G2 / m phase whiIe inducing apoptosis of SmmC-7721 ceIIs. The resuIts of eIectrochemicaI anaIysis showed that BmC and hepatoma SmmC-7721 ceII DNA formed a non-eIectroactive supermoIecuIar compound through the mixed-mode of eIectrostatic interaction and insertion effect. The binding parameters were obtained:the binding number m = 2,the binding constant βBC = 2.77 ×106 L·moI-1 ,βBC-Ni = 5.46 ×106 L·moI-1 ,βBC-Co =7.74×106 L·moI-1 ,and βBC-Cu =1.21×107 L·moI-1 . The abiIity of BmC to bind to DNA was signifi-cantIy enhanced by BC compIexes with metaI ions,and their abiIity was Iisted as foIIows:BC-Cu﹥BC-Co﹥BC-Ni﹥BC. CONCLUSlON BmC shows cytotoxicity by bIocking the ceII cycIe,inhibiting ceII proIiferation and motivaing apoptosis. The abiIity of BmC to bind to DNA is consistent with its cytotoxicity. BmC,after binding to ceII DNA,wiII bIock DNA repIication,inhibit ceII proIiferation,Iead to ceII apoptosis,and exhibit anti-tumor activity.%目的：探讨黄芩苷（BC）-金属（Ni2+，Co2+和 Cu2+）配合物（BmC）与肝癌细胞 DNA 的结合能力与其细胞毒性的关联性。方法络合配位法合成 BmC 并表征其组成和结构；mTT 法、PI 单染法和 AnnexinⅤ-FITC 双染法检测 BmC 对人肝癌 SmmC-7721细胞增殖、周期和凋亡的影响，结合形态学观察探讨其对SmmC-7721细胞的毒性作用；以提取的肝癌 SmmC-7721细胞 DNA 为靶点，采用电化学循环伏安法和交流阻抗法研究 BmC 与 DNA 的相互作用，探讨二者的作用机制。结果成功制备3种新型 BmC，即 BC-铜（BC-Cu）、BC-钴（BC-Co）和 BC-镍（BC-Ni），解析获得配合物的分子式为 Na2 Ni（C21 H16 O11）2·10H2 O， Na2 Co（C21 H16 O11）2·8H2 O 和 Na2 Cu（C21 H16 O11）2·8H2 O；细胞增殖和形态学检测结果显示，BmC 6.25~100 mg·L-1作用24，48和72 h 后，能明显抑制 SmmC-7721细胞增殖，细胞毒性顺序为 BC-Cu﹥BC-Co﹥BC-Ni﹥BC，并存在明显的时间效应和浓度效应关系（P﹤0.01）；细胞周期和凋亡检测结果显示，BmC 使细胞阻滞于 G0/ G1期，阻止进入 S 期和 G2/ m 期，促使 SmmC-7721细胞发生凋亡；电化学分析显示，BmC 与肝癌 SmmC-7721细胞 DNA 通过静电作用和插入作用的混合模式形成非电活性超分子化合物，结合数 m＝2，结合常数βBC ＝2.77×106 L·moI-1，βBC-Ni ＝5.46×106 L·moI-1，βBC-Co ＝7.74×106 L·moI-1和βBC-Cu ＝1.21×107 L·moI-1，BC 与金属离子配位后与 DNA 的结合能力明显增强，强弱顺序为 BC-Cu﹥BC-Co﹥BC-Ni﹥BC。结论 BmC 通过阻滞细胞周期抑制细胞增殖，促进细胞凋亡，表现出细胞毒性作用，且 BmC 与 DNA 结合能力与其细胞毒性一致，具有关联性，表明 BmC 进入 SmmC-7721细胞后与 DNA 结合，阻滞 DNA 复制，抑制细胞增殖，促进细胞凋亡，进而表现出抗肿瘤活性。
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