The Study Of Apoptosis-related Proteins In Colorectal Carcinoma

Objective.We investigate the expression of survivin in colorectal carcinoma(CRC) and its correlation with clinical pathology, and analyze the expressions of survivin ,Bak,Smac/DIABLO,caspase-3 and their important roles in inhibiting apoptosis of CRC.Methods.Survivin mRNA expression was detected by RT-PCR and the expressions of Bak, caspase-3,caspase-9 and Smac/DIABLO proteins were measured using Western blot method in 32 primary colorectal carcinoma and matched normal tissues.Result.(l)Exprssion of survivin mRNA was detected in a significantly greaterproportion of CRC(62.5%) than adjacent normal tissue(25%)(P<0.05).No significant positive correlation of survivin mRNA expression with tumor size,invasive depth,lymph node metastasis anddifferntiation of malignance was observed;(2)There were a 5-fold and 3.5-fold decreases of the activites of caspase-3 and caspase-9 in CRC compared to the asjcent normal tissue;(3)The Smac/DIABLO protein had a 1-fold increase in CRC;and(4)The Bak level was 4.5-fold decrease in CRC than that of adjacent normal tissue.Conclusions. (1)Survivin may regulate apoptosis by:(1)Directly inhibiting thecaspase-3 responsible for induction and execution of apoptosis.(2)Indirectlyinhibiting caspase-3 function by regulating Smac/DIABLO.Decreased Bak protein may inhibit the release of Cyt C and the formation by apopsome resulting indown-regulation of caspase-3 activity through caspase-9.The caspase-3 is effector molecule located at the termini of apoptosis signal pathway to finish the action of killing cells.In summary,the inhibition of apoptosis may exert important role in tumourgenesis for CRC.