雷公藤内酯醇联合5-氟尿嘧啶对结肠癌的作用研究

The evaluation of therapeutic efficacy on combined treatment of human colon carcinoma with triptolide and 5-fluorouracil

目的研究雷公藤内酯醇（TPL）与5-氟尿嘧啶（5-Fu）联合应用对结肠癌细胞增殖、凋亡及瘤体生长的影响并观察其在结肠癌化疗中的毒副作用。方法常规培养HT-29细胞，应用四甲基偶氮唑蓝比色法、流式细胞术检测TPL、5-FU联合应用对人结肠癌细胞增殖和凋亡的影响；中效原理评价两药的联合作用；建立裸鼠荷人结肠癌动物模型，分别及联合应用0．25mg／（kg·d）TPL和12mg／（kg·d）5-FU对其进行治疗，观察荷瘤裸鼠一般情况、瘤体的生长及化疗毒副作用。结果（1）TPL和5-FU分别及联合应用，在一定浓度范围内对结肠癌细胞有明显的增殖抑制和诱导凋亡作用，并且联合用药作用明显强于单独用药，48h凋亡率高达（41．71±1．38）％；（2）TPL和5-Fu单独应用均可抑制结肠癌瘤体的生长，肿瘤抑制率分别为78．53％、84．16％；2者联合应用时作用更为明显，肿瘤抑制率达96．78％；（3）整个化疗过程中除偶尔出现全身散在红斑、丘疹外，未见明显造血系统、肝肾功能损害等毒副作用。结论TPL与5-Fu联合应用比单独应用对结肠癌细胞株增殖抑制作用更强；TPL与5-FU在小剂量联合应用时协同抑制肿瘤细胞增殖，抑制瘤体生长，并能促进结肠癌细胞凋亡，在体外实验中毒副作用小。

Objective To investigate the inhibitive effects of triptolide （TPL） combined with 5 -fluorouracil （5-FU） on colon carcinoma in vitro and in vivo, and the side effects of the two drugs during the chemotherapy for colon carcinoma. Methods The human colon carcinoma HT - 29 cells were cultured with RPMI 1640 medium. The effects of TPL combined with 5 - FU or alone on HT - 29 cells were examined by MTT assay, flow cytometry. The combined effects of TPL and 5 - FU were evaluated by the median - effect principle. The animal model of human colon carcinoma was established in nude mice. 0.25mg/（kg·d） TPL combined with 12mg/（ kg·d） 5 -FU or alone were injected intraperitoneally to mice, the inhibitive effects and the side effects of the drugs were observed. Results Either combined TPL and 5 - FU or alone inhibited significantly the proliferation of colon carcinoma cells and induced obvious apoptosis. The combined effects of two drugs were more effective than either drug alone （ apoptic rate of 48 hours 41.71± 1.38% ）. The combined effects of the two drugs were synergistic （CI 〈 1 ） at lower concentrations. TPL or 5 - FU alone inhibited significantly the growth of colon carcinoma cells when transplanted into nude mice and the tumor inhibition rates were 78.53% and 84.16%. Combination of the two drugs had more significant effect, as the tumor inhibition rate reached 96.78%. During the course of chemotherapy, no obvious side effect was observed. Conclusion The inhibitive effects of TPL combined with 5 - FU on the growth of human colon carcinoma in vitro and in vivo are superior to using TPL or 5 - FU alone. TPL combined with 5 - FU has synergistic effects at lower concentrations and promotes aDontosis, but does not increase side effects of chemotherapy.