Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3

Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured.results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced.Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer.Inhibition of apoptosis is one of the important mechanisms for the growth of many malignant tumor cells. IAPs, the new anti-apoptotic protein families which independent of Bcl-2, are a hot apoptosis research field in recent years, and can play an important role in inhibiting tumor cell growth. Until now, 8 members of IAPs family were found: NAIP[1], ILP-2[2], c-IAPl(MIHB, HIAP-2), c-IAP2((HIAP-1, MIHC, API2)[3], XIAP(hILP, MIHA, ILP-1)[4], Bruce(apollon)[5], survivin[6] and Livin(ML-IAP, KIAP)[7]. Livin as a new member of IAPs family was found in recent years, which shows high expression level in some specific tumor tissue cells, but little, if not none, in normal tissues. Researchers had found that it may become the target for tumor therapy [8,9]. In 2003, Gazzaniga et al [10] used RT-PCR in 30 cases of transitional cell carcinoma of the bladder (TCCB) tumor tissue to detect Livin mRNA expression level, and the results showed that normal bladder tissues did not express Livin, while TCCB tissues expressed high level of Livin. They made a