A potential novel combination therapy targeting survivin in renal cancer cells: Inhibition of survivin expression by topotecan and hexamethylene bisacetamide

Survivin is an inhibitor of apoptosis and, as it is found in many tumors but not in most normal differentiated tissues, is an attractive target for cancer therapy. Survivin expression has been associated with cell proliferation in renal cancer. We previously demonstrated the possibility of treating renal cancer by suppressing survivin expression using the topoisomerase I inhibitor topotecan and survivin-specific siRNA. In the present study, we used Caki-1 cells to investigate the possibility of treating renal cancer by combining topotecan and the hybrid polar compound hexamethylene bisacetamide (HMBA) to completely suppress survivin expression. HMBA is known to induce cell differentiation. This warrants the testing of the ability of HMBA to suppress survivin, which is associated not only with carcinogenesis but also with differentiation. Both topotecan and HMBA were shown to suppress survivin expression and cell proliferation. However, the combination of topotecan and HMBA suppressed survivin expression completely and more effectively inhibited cell proliferation, leading to apoptosis. Combination therapy using topotecan and HMBA might thus be effective treatment for advanced renal cancer.