姜黄素联合奥沙利铂对人结肠癌LoVo细胞裸鼠移植瘤的抗癌作用研究

目的 探讨姜黄素与奥沙利铂联用对人结肠癌LoVo细胞株裸鼠移植瘤生长的影响及其作用机制.方法 将LoVo细胞接种子裸鼠皮下,制备裸鼠移植瘤模型.将造模成功的裸鼠随机分为对照组、姜黄素50 mg/kg组、奥沙利铂25 mg/kg组、姜黄素50 mg/kg+奥沙利铂25 mg/kg联合给药组,给药组裸鼠隔天ip给药1次,连续给药11次.末次给药后剥离瘤块称质量,计算移植瘤体积、抑瘤率;摘除眼球取血,检测血常规及肝、肾功能;流式细胞仪检测肿瘤细胞周期和凋亡率;HE染色分析肿瘤组织病理形态学;RT-PCR检测细胞凋亡相关基因的表达.结果 姜黄素组、奥沙利铂组、联合用药组的抑瘤率分别为59.47％、55.49％、70.56％,联合给药组抑制肿瘤生长的作用显著且对荷瘤裸鼠血液及肝肾无明显毒性;联合给药组可显著阻滞肿瘤细胞于S期和G2/M期,显著上调bax基因的表达.结论 姜黄素联合奥沙利铂可显著抑制LoVo细胞裸鼠移植瘤的生长.

Antitumor effects of curcumin and oxaliplatin combination on xenografts of human colon cancer LoVo cells in nude mice

Objective To investigate the effects of curcumin combined with oxaliplatin on the human colon cancer cells LoVo xenografted tumor in nude mice and to explore the mechanism. Methods Nude mice were implanted with human colon cancer LoVo cells. All tumor-bearing mice were randomly divided into four groups and treated with vehicle, 50 mg/kg curcumin, 25 mg/kg oxaliplatin, and their combination (50 mg/kg curcumin + 25 mg/kg oxaliplatin) by ip injection once every other day individually. After continuous administration of drug treatment for 11 times, the weights of nude mice were recorded, the stripping tumor weight was monitored, and the tumor volume and tumor inhibitory rates were calculated. The enucleation of eyeball for taking blood and blood routine examination were carried out and the function of liver and kidney was detected. Tumor cell cycle and apoptosis rate were assayed by flow cytometry. The pathological morphology of tumor was analyzed by HE staining. The apoptosis related gene expression was detected by RT-PCR. Results Tumor inhibitory rates of curcumin, oxaliplatin, and curcumin + oxaliplatin groups were 59.47%, 55.49%, and 70.56%, respectively. Curcumin combination with oxaliplatin did not influence the blood system, liver, and kidneys in nude mice. Combination of curcumin and oxaliplatin could effectively inhibit the tumor growth (P < 0.05), interfere with cell cycle arresting at S and G₂/M phases (P < 0.05, 0.01), and promote the expression of bax (P < 0.01) in tumor-bearing nude mice. Conclusion Combination of curcumin and oxaliplatin could synergistically inhibit the growth of LoVo colonic xenografts in nude mice.