Abstract
Background: Survivin is a negative regulator of apoptosis. We evaluated the efficacy of YM155, a selective suppressant of survivin, in combination with gemcitabine in the pancreatic cancer cell line MiaPaCa-2. Materials and Methods: Expression of survivin was demonstrated by immunoblotting. Cell cycle progression was determined by flow cytometric analysis. Cell viability was assayed using the trypan blue exclusion assay. Results: Gemcitabine upregulated survivin expression, whereas treatment with YM155 suppressed the expression of survivin. Concomitant treatment with YM155 enhanced chemosensitivity to gemcitabine, which was accompanied by a decrease in the expression of survivin. Knockdown of endogenous survivin via RNA interference also enhanced the sensitivity to gemcitabine. In addition, YM155 potentiated the antitumor effect of gemcitabine in xenograft tumors of MiaPaCa-2. Conclusion: YM155 potentiates chemosensitivity to gemcitabine in pancreatic cancer cells by suppressing the induction of survivin. Combination treatment with gemcitabine and YM155 may be a potential therapeutic strategy for the treatment of pancreatic cancer that warrants further clinical investigation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1681-1688 |
| Number of pages | 8 |
| Journal | Anticancer Research |
| Volume | 32 |
| Issue number | 5 |
| State | Published - May 2012 |
Keywords
- Gemcitabine
- In vivo model
- MiaPaCa-2
- Pancreatic cancer
- Survivin
- Xenograft
- YM155
