辣椒碱对乳腺癌MDA-MB-231细胞裸鼠移植瘤生长的抑制作用

Inhibitory Effect of Capsaicin on Growth of Breast Cancer MDA-MB-231 Cells Transplanted Tumor in Nude Mice

目的:观察辣椒碱对乳腺癌MDA-MB-231细胞裸鼠移植瘤生长的抑制作用及其机制。方法:通过皮下注射MDA-MB-231细胞的方法建立乳腺癌裸鼠移植瘤模型,待肿瘤体积达到约100 mm3,将裸鼠随机分为模型组和辣椒碱低、中、高剂量(5,10,20 mg·kg^(-1))组,每组5只。辣椒碱低、中、高剂量(5,10,20 mg·kg^(-1))组裸鼠分别腹腔注射相应剂量的辣椒碱,模型组注射等体积的磷酸缓冲盐溶液(PBS)溶剂,3 d/次,连续给药8次。每次给药前先检测裸鼠体质重和肿瘤体积,末次给药24 h后处死各组裸鼠,计算肿瘤体积,称肿瘤质量,并计算抑瘤率。应用免疫组化法和蛋白免疫印迹法(Western blot)检测辣椒碱治疗后各组肿瘤组织中高迁移率族蛋白B1(HMGB1)和Toll样受体4(TLR4)蛋白表达水平。结果:与模型组比较,辣椒碱低、中、高剂量(5,10,20 mg·kg^(-1))组裸鼠体质量无明显变化,但肿瘤体积显著缩小(P <0. 01),肿瘤质量显著减小(P <0. 01),抑瘤率显著增大(P <0. 01),且呈剂量依赖性;与模型组比较,辣椒碱低、中、高剂量(5,10,20 mg·kg^(-1))组肿瘤组织HMGB1和TLR4蛋白表达明显降低,且呈剂量依赖性。结论:辣椒碱对乳腺癌MDA-MB-231细胞裸鼠移植瘤生长具有明显的抑制作用,其机制可能与下调HMGB1和TLR4蛋白表达有关。

Objective:To investigate the inhibitory effect of capsaicin on the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice and its possible molecular mechanism.Method:Transplanted tumor model of breast cancer MDA-MB-231 cells in nude mice were established.Then the tumorbearing mice were randomly divided into 4 groups:model group,and low,medium and high-dose capsaicin groups(5,10,20 mg·kg^-1).Mice of low,medium and high-dose capsaicin groups(5,10,20 mg·kg^-1)were intraperitoneally injected with the corresponding dose of capsaicin,and the model group was injected with the same volume of phosphate buffer saline(PBS),once every 3 days,for a total of 8 times in succession.Body weight of mice and transplantation tumor volume were measured before each injection of capsaicin.Mice of each group were put to death 24 h after the last administration,and then the tumor volume,mass and the tumor inhibitory rate were calculated.The protein expression levels of high mobility group box 1(HMGB1)and Toll-like receptors 4(TLR4)were measured by immunohistochemistry and Western blot.Result:No significant difference was observed between each group in body weight.However,compared with the model group,capsaicin(5,10,20 mg·kg^-1)remarkably inhibited the tumor volume and mass(P<0.05,P<0.01),and increased the tumor inhibitory rate(P<0.01)in a dose-dependent manner.Capsaicin(5,10,20 mg·kg^-1)also markedly inhibited the protein expression levels of HMGB1 and TLR4(P<0.01).Conclusion:Capsaicin remarkably inhibits the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice,and the possible mechanism may be related to the down-regulation of HMGB1 and TLR4 at the protein level.