摘要
目的探讨蛋白酶体抑制剂MG132对肿瘤恶病质的作用及其可能的分子机制。方法经小鼠腋窝皮下注射结肠腺癌C26细胞,建立肿瘤恶病质模型,并设正常对照组(HC组)。将模型小鼠分为肿瘤恶病质组(CC组)和MG132治疗组(MG组),待小鼠进入恶病质状态后,CC组小鼠经腹腔注射0.1 ml生理盐水,MG组小鼠经腹腔注射0.1 mg/kg的MG132,7 d后处死小鼠,称量小鼠肿瘤、左侧腓肠肌和附睾脂肪的重量,测量腓肠肌纤维横切面积,ELISA法检测血清中炎性因子TNF-α和IL-6的水平,RT-PCR及Western blot法检测腓肠肌中IKBa、P65、MuRF1和MAFbx基因mRNA的转录水平及蛋白的表达水平。结果与CC组相比,MG组小鼠腓肠肌和附睾脂肪组织的重量分别增加了31.6%和39.5%(P<0.05),腓肠肌纤维横切面积增加了36.1%(P<0.05);血清中TNF-α和IL-6的水平分别降低了20.9%和42.0%(P<0.05);腓肠肌组织IKBa基因mRNA的转录水平和蛋白表达水平分别升高了132.7%和56.5%(P<0.05),MuRF1基因mRNA的转录水平和蛋白表达水平分别降低了70.1%和42.6%(P<0.05),MAFbx基因mRNA的转录水平和蛋白表达水平分别降低了76.8%和47.3%(P<0.05),P65基因mRNA的转录水平和蛋白表达水平分别降低了59.1%和53.1%(P<0.05)。结论 MG132改善肿瘤恶病质的分子机制可能与抑制NF-κB途径及MuRF1和MAFbx的表达、抑制炎症反应及肿瘤生长有关。
Objective To investigate the function and possible molecular mechanism of protease inhibitor MG132 in cancer cachexia. Methods Twenty-four male BALB/c mice were divided into healthy control （HC）, cancer eaehexia （CC） and MG132 treatment （MG） groups. The mice in HC group were uninjected, while those in CC and MG groups were injected s.c. with colon adenoearcinoma C26 cells to establish the mouse model of cancer cachexia. The model mice in MG group were injected i.p. with O. 1 mg/kg MG132, while those in CC group with 0. 1 ml physiological saline. The mice in various groups were killed 7 d after treatment, of which the tumor, left gastrocnemius muscle and epididymis adipose tissue were weighed, the fiber crosscut area of gastrocnemius muscle was measured, the TNF-α and IL-6 levels in sera were determined by ELISA, while the mRNA transcription and protein expression levels of IkBa, P65, MuRF1 and MAFbx were determined by RT-PCR and Western blot respectively. Results Compared with those in CC group, the weights of gastrocnemius muscle and epididymis adipose tissue of mice in MG group increased by 31. 6% and 39. 5% respectively（P 〈 0. 05）, the fiber crosscut area of gastrocnemius muscle increased by 36. 1% （P 〈 0. 05）, while the TNF-a and IL-6 levels in sera decreased by 20. 9% and 42. 0% respectively （P 〈 0. 05）; however, the mRNA transcription and protein expression levels of IKBa in gastrocnemius muscle increased by 132. 7% and 56. 5% respectively （P 〈 0. 05）, while those of MuRF1 decreased by 70. 1% and 42. 6%（P 〈 0. 05）, those of MAFbx decreased by 76. 8% and 47. 3% （P 〈 0. 05）, and those of P65 decreased by 59. 1% and 53. 1%, respectively （P 〈 0. 05）. Conclusion The molecular mechanism of MG132 in improving cancer cachexia may be related to the inhibitions of NF-KB pathway, MuRF1 and MAFbx expressions, inflammatory reaction and tumor growth.
出处
《中国生物制品学杂志》
CAS
CSCD
2013年第3期372-376,共5页
Chinese Journal of Biologicals
基金
重庆市卫生局医学科研计划项目(2011-2-101)
