Carfilzomib ameliorates hepatic function in mice with cancer cachexia and its molecular mechanism / 中华内分泌外科杂志

ABSTRACT

Objective To study the role of CFZ in the amelioration of hepatic function in cancer cachexia and its associated mechanism.Methods Forty BALB/c mice were selected.BALB/c mice were divided into 4 groups randomly,including a healthy control group (HC),a CFZ prevention group (CP),a CFZ treatment group (CT) and a cancer cachexia group (CC).Cancer cachexia model was induced by injecting murine colon 26 adencarcinoma cells into male BALB/c mice intraperitoneally.Following administration of CFZ intraperitoneally twice a week to CP and CT groups on the days 5 and 12 after tumor cells injection,respectively,all mice were acrificed on day 19.hepatic function was detected by automatic biochemistry analyzer,The concentration of inflammatory cytokines and CRP were detected by ELISA.The mRNA and protein expression of IκBα and p65 were detected by real-time PCR and western blotting.Results Compared with HC group,CP group and CT group,the albumin in CC group was significantly decreased,and the concentration of glutamate transaminase,total bilirubin,direct bilirubin and triglyceride were significantly increased,(221.67±12.38)U/L、(315.53±13.60)U/L、(1.65±0.32)mmol/L、(0.88±0.21) mmol/L、(4.98±0.32)mmol/L respectively.Liver biochemical test of CP group [(108.27±16.55)U/L、(180.45±15.28)U/L、(1.15±0.27) mmol/L、(0.58±0.12) mmol/L、(2.93±0.18) mml/L) and CT group [(148.56± 18.16)U/L、(247.18±21.64)U/L、(1.34±0.19) mmol/L、(0.69±0.16) mml/L、(3.75±0.28) mmol/L] was improved after CFZ treatment,and CP group was better than that of CT group.The concentrations of TNFa,IL-1,IL-6 and CRP in CC group [(156±9.56)ng/L、(762±9.46)ng/L、(962±9.12) ng/L、(772±10.04 ng/L)] were significantly higher than those in HC group[(16.42±5.63ng/L、174±9.61 ng/L、206±8.27 ng/L、397±10.2 ng/L)],CP group[(71.25± 4.41 ng/L、398±9.72 ng/L、398±9.72 ng/L、483±9.71 ng/L)] and CT group [(113±8.01 ng/L、506±8.74 ng/L、703± 7.76ng/L、651±11.31 ng/L)].The expression of IκBα in HC group,CP group and CT group were higher than that in CC group,and the difference was statistically significant.The expression of IκBαwas was more obvious in CP group than that in CT group.Compared with HC group,the expression of p65 in CP group,CT group and CC group was significantly increased,respectively,and the difference was statistically significant.The expression of p65 in CP group was lower than that in CT group(P=0.000).Conclusion CFZ ameliorates hepatic function in cancer cachexia mice,which may be related to the inhibition of NF-κB resulting in liver function improvement,the inhibition of tumor growth and the consumption of skeletal muscle.