Research Of The Role Of Caspase3in Cancer Cachexia Skeletal Muscle Protein Consumption

Objective: This study by building model of BALB/c mice tumorcachexia,Observation of the changes when mice be injected Caspase3inhibitors (Z-VAD–FMK), To study the role of caspase3in cancercachexia skeletal muscle protein consumption.Methods:（1） Murine Colon26adenocarcinoma cells wereinoculated in male BALB/c mice to establish models of cancercachexia．Body weight were detected daily. The left gastrocnemius muscleweight, Fiber crosscut area, levels of TNF-α、IL-6, the protein levels ofCaspase-3, the apoptosis levels of muscle cells were tested on day8,14and20.（2）122BALB/c mice were randomly divided into control group(HC，n=8), cancer cachexia(CC,n=38), cancer injected Physiological saline(INS,n=38),and Caspase-3inhibitor group(IC,n=38). Murine Colon26adenocarcinoma cells were inoculated in mice of CC group and IC group toestablish models of cancer cachexia．Caspase-3inhibitor(Z-VAD-FMK)were intraperitoneal injected to IC group1.5mg/kg/d, and equivalent dose normal saline to CC group from the13th day.8mice were sacrificed ineach group in the21st day. Tumor weight, body weight removed tumor, leftgastrocnemius muscle weight and its fiber crosscut area were detected ineach group. The apoptosis rate of left gastrocnemius muscle and tumortissue in each group were tested by TUNEL. Caspase-3protein level weretested by Western blot individually. Microvessel density(MVD) in eachgroup were marked by CD34. The remaining mice were intervenedpreviously and recorded the survival time.Results：（1）1.Compared with the control group, body weight,non-tumor body weight, fiber crosscut area and weight of the leftgastrocnemius muscle were obviously decreased（P<0.05），whereas levelsof TNF-α、IL-6, protein levels Caspase3and the apoptosis levels ofmuscle cells were obviously increased after tumor inoculation（P<0.05）.The level of Caspase3or the apoptosis rate of muscle cellswas positively correlated and the consumption of gastrocnemius musclerespectively（P<0.05）.（2）Compared with CC group, body weight removed tumor、leftgastrocnemius muscle weight and its fiber crosscut area, and survivial timewere significantly increased in IC group（P<0.05）；tumor weight, theapoptosis rate of left gastrocnemius muscle, Caspase-3protein level in leftgastrocnemius muscle and MVD in the tumor were obviously decreased inIC group respectively（P<0.05）. But the apoptotic index of each group had no significant difference（P>0.05）Conclusions：1. Caspase-3may play an important role in cancercachexia skeletal muscle protein comsumption.2. Caspase-3inhibitor can inhibit skeletal muscle protein consumptionin cancer cachexia, restrain the angiogenesis in tumor, thus improve thesurvival condition and prolong the survival time in cancer cachexia.