Relationships Between Induction Of Apoptosis By CDDP In Scaber Cell And Apoptosis-related Proteins

Apoptosis is a process of cell death that actively carries out the suicide process under the control of a series of gene regulators. The occurance and development of tumor are the result the ability of loss in apoptosis of tumor cells.Thus,the effectiveness of anticancer drugs may not simply reflect their ability to cause cellular damage,but also the cell's ability to detect and respond to this damage.However,until recently,the tumor-specific toxicity of most anticancer agents wasattributed to their debilitating effects on actively proliferating cells.Most recently,it hasbecome apparent that most anticancer agents induce apoptosis.Current evidences suggest that apoptosis is controlled by genes such as bcl-2,bax,PCNA,P53,caspase-3 et al .pro- and anti-apoptosis of these proteins werecontroversial.Together taken,in this study,we examined the expression levels of apoptosis-relatedproteins bcl-2,bax.PCNA,P53,Caspase-3 and to determine the relationship between theirchanges and apoptosis.To investigate the effect of cisplatin as well as in combination with a-TNF on apoptosis in Scaber cell. The apoptotic cells were detected by TUNEL,HE,eletronic micrpscopy .The results followed as: Treatment of Scaber cells with CDDP resulted in characteristics typical of apoptosis .a-TNF induced apoptosis of Scaber cells with time and concentration increase in apoptotic cell index. The synergistic effect of CDDP incombination with a-TNF were observed. Apoptosis was not observed in Scaber cells treated with Fas antibody (SC-175).Taken together, All of CDDP and a-TNF may induced apoptosis in Scaber cell. To further investigate the mechanism of apoptosis induced by CDDP. The expressions and activity of apoptosis-associated proteins such as bcl-2, bax, P53, PCNA, and caspase-3 were examined using S-P method.The rrsults showed: CDDP caused time-and concentration -dependent decreases in bcl-2 and increased in bax proteins.CDDP gave rose to decreases in bcl-2 and its translocation to perinuclei and nuclei. In contrast to untreated Scaber cell, which express low PCNA , Scaber cells treated with CDDP caused the decrease of PCNA in Scaber. The expression of caspase-3 in Scaber cell were determined during apoptosis induced by CDDP.In conclusion,our investigetion showed that the apoptosis induced by CDDPis related to the increase of bax protein and the decrease of bcl-2 protein, and its translocation to perinuclei and nuclei.