siRNA-mediated inhibition of antiapoptotic genes enhances chemotherapy efficacy in bladder cancer cells.

BACKGROUND

The up-regulation of antiapoptotic B-cell CLL/lymphoma 2 (BCL2), BCL2-like 1 (BCLXL), X-linked inhibitor of apoptosis (XIAP) and survivin is one mechanism by which cancer cells develop resistance towards chemotherapeutics. Therefore, the knockdown of these four genes could sensitise bladder cancer (BCa) cells towards chemotherapy.

MATERIALS AND METHODS

BCL2, BCLXL, XIAP and survivin were inhibited using siRNAs--either one target-alone or all four targets simultaneously--in EJ28 and J82 BCa cells. After 24 h, cells were treated with mitomycin C or cisplatin. Treatment effects were analysed regarding cell viability, cell count and apoptosis induction.

RESULTS

Knockdown of BCLXL and survivin, as well as the simultaneous inhibition of all four antiapoptotic genes, sensitised EJ28 and J82 cells towards mitomycin C and cisplatin.

CONCLUSION

Since the contribution of one antiapoptotic gene to chemotherapy response can vary between BCa cell lines, the simultaneous knockdown of multiple inhibitors of apoptosis might represent a more promising option for enhancing chemotherapy efficacy in BCa treatment.