胰岛素增加肿瘤细胞化疗敏感性的研究

The effect of insulin on the chemosensitivity of cancer cells

目的 探讨胰岛素对肿瘤细胞化疗敏感性的影响及机制.方法 以胰岛素和甲氨蝶呤（MTX）或5-氟尿嘧啶（5-Fu）处理人结肠癌细胞SW480,小鼠结肠癌细胞CT-26及小鼠乳腺癌细胞4T1,噻唑蓝（MTT）法分析细胞活力,荧光显微镜和流式细胞术观察肿瘤细胞对荧光标记MTX的摄取,并利用小鼠荷瘤模型,观察胰岛素及低MTX糖对MTX化疗疗效的影响.结果 （1）胰岛素增加MTX和5-Fu的细胞毒作用4.1%-11.5%.（2）胰岛素增加肿瘤细胞对MTX摄取141.9%.（3）胰岛素及低血糖状态增强MTX抑瘤作用20.1%.结论 胰岛素及低血糖状态增加肿瘤细胞对化疗药物的吸收,提高肿瘤细胞对化疗药物的敏感性.

Objective To investigate the effect and mechanism of insulin and hypoglycemia on the chemosensitivity of cancer cells. Methods Human colon cancer cells SW480, mouse colon cancer cells CT-26 and mouse breast cancer cells 4T1 were cultured and treated with insulin and chemotheraputic drugs, 5-fluorouracil or methotrexate. MTT assay was used to measure the cytotoxity. Fluorescence microscopy and flow cytometry were used to determine the effects of insulin on the uptake of fluorescent methotrexate by cancer cells. Mouse breast cancer cells 4T1 were inoculated into syngeneic BALB/C mice. Insulin was administrated to the mice before giving methotrexate and the therapeutic effect was monitored. Results （1） Insulin enhanced the chemocytotoxity of chemotheraputic drugs on cancer cells by 4. 1% to 11.5%;（2） Insulin increased the uptake of fluorescent methotrexate by cancer cells in vitro by 141. 9% ;（3） Insulin and hypoglycemia enhanced the chemotherapeutic effect of methotrexate on mouse breast cancer models by 20. 1%. Conclusion Insulin and hypoglycemia increase absorption of chemotherapeutic agents by cancer cells and enhance the chemosensitivity of cancer cells.