丹酚酸A抑制核苷转运并增强化疗药物的抗肿瘤作用

Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor activity of chemotherapeutic drugs

目的 观察丹酚酸A(SAA)的抑制核苷转运活性及其抗肿瘤作用。方法 用3H TdR和3H UR转运测定法 ,克隆生成测定法以及小鼠移植性肉瘤 180模型。结果 SAA抑制艾氏腹水癌细胞的胸苷和尿苷的转运 ,其IC50 分别为 18 1和 17 1μmol·L- 1 。SAA能明显增强 5 FU、丝裂霉素C、MTX对KB细胞、肝癌BEL 74 0 2细胞的细胞毒性。体内试验 ,SAA 2 0 0mg·kg- 1 和 5 FU 10mg·kg- 1 单独使用的抑瘤率分别为 4 1%和 2 7% ;SAA和 5 FU联合使用的抑瘤率为 6 3% (CDI=0 86 )。结论 SAA有抑制肿瘤细胞核苷转运的活性 ,可增强 5 氟尿嘧啶等药物的抗肿瘤作用 。

Aim To investigate the inhibitory activity of salvianolic acid A (SAA) on nucleoside transport in cancer cells and its antitumor effect. Methods [ 3H]thymidine and [ 3H]uridine transport assays were used to determine the inhibitory activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to cultured cancer cells was examined with clonogenic assay. The antitumor effect in vivo was evaluated with transplantable tumor model in mice. Results SAA was shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with IC 50 values of 18.1 and 17.1 μmol·L -1, respectively. By clonogenic assay, the IC 50 of SAA for KB cells was 44.7 μmol·L -1. SAA markedly potentiated the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180 cells were transplanted sc in mice and tested drugs were administered ip. When administered separately, SAA at 200 mg·kg -1 and 5-FU at 10 mg·kg -1 inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs inhibited tumor growth by 63% (CDI=0.86). Conclusion SAA is active in blocking nucleoside transport in cancer cells and potentiates the cytotoxicity of chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo, SAA might be useful in combination cancer therapy.