摘要
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.
出处
《中国医药》
2008年第1期5-7,共3页
China Medicine
基金
基金项目:湖北省卫生厅科研基金资助项目(JX3822)