左旋棉酚联合多西紫杉醇治疗肺癌

Combination of （-）-gossypol and docetaxel for lung cancer

目的 观察左旋棉酚（LG）联合多西紫杉醇（DOC）对肺癌治疗的体内体外影响,探讨两者是否具有协同作用及其机制.方法 LG（3、5μmol/L）联合DOC（0.1、1.0 nmoL/L）作用于A549、A549/DDP和A549/T肺癌细胞,采用噻唑蓝（MTT）法和流式细胞仪法分别检测细胞增殖抑制和凋亡诱导作用;建立C57 BL/6J小鼠肺癌Lewis细胞皮下移植瘤模型,将移植瘤小鼠随机分成7组,每组15只,分别为DOC治疗组（1、2 mg/kg）、LG治疗组（3、5 mg/kg）、联合治疗组（3 mg/kg LG＋1 mg/kg DOC、5 mg/kg LG ＋2 mg/kg DOC）和阴性对照组,进行疗效分析.结果 低剂量联合组对A549、A549/DDP和A549/T的增殖抑制率分别为（67.3±3.1）％、（64.8±2.8）％、（54.1±3.3）％,细胞凋亡率分别为（50.2±1.8）％、（52.3±1.5）％、（42.8±2.4）％;高剂量联合组的增殖抑制率分别为（71.8±1.9）％、（72.4±2.1）％、（60.7±2.6）％,细胞凋亡率分别为（53.2±1.8）％、（55.1±1.9）％、（46.7±2.6）％;高低剂量联合组对肺癌细胞的增殖抑制率和细胞凋亡率均比单独使用DOC显著增加（P＜0.05）,且联合指数（CI）均小于0.5,表现出强大的协同作用.低高剂量联合组小鼠肺癌Lewis细胞移植瘤的肿瘤抑制率分别为49.23％和66.87％,明显高于DOC治疗组.结论 LG与DOC的联用对肺癌细胞的增殖抑制及诱导凋亡具有协同作用,对克服肿瘤细胞耐药性有良好的效果,对小鼠肺癌Lewis细胞移植瘤有明显的抑制作用,且比单独用药效果显著.

Objective To study the effects of （-）-gossypol （LG） combined with docetaxel （DOC） for lung cancer by in vivo and in vitro experiments.Methods The inhibition rate of LG （3 and 5 μmol/L） and DOC （0.1 and 1.0 nmol/L） on proliferation of lung cancer cells （A549,A549/DDP and A549/T） was evaluated using methyl thiazolyl tetrazolium （MTT） method,and the cell apoptosis was measured by flow cytometry.C57 BL/6J mice xenograft models were established with Lewis cells.Fifteen mice were randomly divided into 7 groups,including DOC （1 and 2 mg/kg）,LG （3 and 5 mg/kg）,combined therapy groups （3 mg/kg LG ＋ 1 mg/kg DOC,5 mg/kg LG ＋ 2 mg/kg DOC） and control group,The therapeutic effects were observed.Results In the low dose combination group,the proliferation inhibition rate of lung cancer cells （A549,A549/DDP and A549/T） was （67.3 ± 3.1） ％,（64.8 ± 2.8） ％ and （54.1 ± 3.3） ％,and apoptosis rate was （50.2 ± 1.8） ％,（52.3 ± 1.5） ％ and （42.8 ± 2.4） ％,respectively.In the high dose combination group,the proliferation inhibition rate was （71.8 ± 1.9）％,（72.4±2.1）％ and （60.7 ±2.6）％,and apoptosis rate was （53.2 ± 1.8）％,（55.1 ± 1.9）％ and （46.7 ± 2.6）％,respectively.The proliferation inhibition rate and the apoptosis ratio in combination group were significantly increased （P ＜ 0.05）,and CI was less than 0.5 （interpretation strong synergism）.In the low and high dose combination group,the tumor inhibition rate was 49.23％ and 66.87％ respectively,which was higher than in the DOC therapy group significantly.Conclusion Combination of LG and DOC has synergistic effect on inhibition of tumor proliferation and apoptosis induction of lung cancer cells,and has favorable effect on surmounting drug resistance of lung cancer,could inhibit mice xenograft tumor of Lewis lung cancer significantly and exert more significant effect than used alone.