The effect of antisense survivin-liposome complex on cell growth, apoptosis and cell cycle in hepatocellular carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects and the mechanisms of cell growth inhibition in hepatocellular carcinoma cells after induction with antisense survivin-liposome (LIP) complex, and to provide evidence in treatment for hepatocellular carcinoma and tumors expressing survivin.</p><p><b>METHODS</b>Survivin ODNs was transfected into HepG2 cells mediated by LiP reagent. The expression of survivin mRNA and protein was detected by RT-PCR and Western blot. MTT assay was applied to determine cell proliferation in HepG2 cells. Active caspase-3 and apoptosis rate were evaluated by flow cytometric analysis. The morphological changes were assessed by electron microscopy. Cell cycle was analyzed by flow cytometry in the cell cycle-synchronized hepatocellular carcinoma cells treated with the antisense compound.</p><p><b>RESULTS</b>Antisense compound efficiently down-regulated survivin expression (mRNA and protein) in a dose-dependent manner with an IC(50) of 250 nmol/L. Its maximal effect was achieved at a concentration of 600 nmol/L, when expression levels were down-regulated by 80%, as revealed by gradually increase of caspase-3-like protease activity and apoptosis rate in a time-dependent manner. Morphological apoptotic changes such as membrane blebbing, loss of microvilli, cytoplasmic vasculization, condensation of cytoplasm and nucleus, chromatin fragmentation, and apoptosis and cell growth inhibition were observed. In the cell cycle-synchronized hepatocellular carcinoma cells, antisense compound induced cell cycle arrest followed by apoptosis. After treated with low concentration of compound, the cell cycle was arrested at S phase or G2/M phase; while at high concentration, the cell cycle was mainly arrested at S phase. Apoptosis was obviously observed and the rate of apoptosis was increased in a time and concentration-dependent manner.</p><p><b>CONCLUSION</b>Antisense survivin has significant inhibitory effect on growth of hepatocellular carcinoma cells in vitro. This is associated with cell cycle arrest and apoptosis.</p>

Prognostic significance of survivin splicing variants in expression gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the expression and associations of three survivin splicing variants in gastric cancer and normal gastric mucosa, and to evaluate the prognostic significance.</p><p><b>METHODS</b>Real time quantitative RT-PCR was used to detect the expression of three survivin splicing variants in tumor and matched normal gastric mucosa specimens from 77 cases with gastric cancer.</p><p><b>RESULTS</b>The expression of three survivin splicing variants than upregulated significantly in gastric cancer than those in normal mucosas (P< 0.01). In cancer tissues, the expression rates of survivin, survivin-2B, survivin-deltaEx3 were 100%, 79.8% (61/77), 64.9% (50/77) respectively. The survival rate was significantly lower in the patients with high survivin expression than those with low survivin expression (P< 0.01).</p><p><b>CONCLUSION</b>Among three survivin splicing variants, the expression level of wild-type survivin mRNA is an important predictor for prognosis.</p>