Topotecan and small interfering RNA suppress survivin expression synergistically in Caki-1 renal cancer cells: Direct suppression of survivin and enhancement of transfection efficiency by topotecan.
Survivin is an apoptosis inhibitor found in many tumors but not in most normal differentiated tissues, which makes it an exciting target for cancer therapy. Survivin expression has been shown to be associated with cell proliferation in renal cancer and we previously demonstrated the possibility of treating renal cancer with survivin-specific siRNA and topotecan, which increased the uptake of siRNA by KU19-20 renal cancer cells. We found in the present study that the combination of siRNA and topotecan inhibits survivin expression in Caki-1 renal cancer cells by another mechanism. Caki-1 renal cancer cells expressed higher level of survivin than KU19-20 cells did and survivin-specific siRNA alone suppressed survivin expression only slightly. The combination of topotecan and siRNA suppressed survivin expression completely and inhibited cell proliferation. Topotecan itself did not increase cellular uptake of siRNA but suppressed survivin expression. It also increased transfection efficiency without increasing cellular uptake of siRNA. Although the mechanism of action varies between cell lines, combination therapy using topotecan and siRNA should offer an attractive approach for treatment of advanced renal cancer.
Sato
Akinori
A
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. zenpaku@ndmc.ac.jp
Ito
Keiichi
K
Asano
Takako
T
Sumitomo
Makoto
M
Asano
Tomohiko
T
Hayakawa
Masamichi
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology*; D000077022:Survivin; D019772:Topotecan / Q000494:pharmacology*; D014162:Transfection
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D019772:Topotecan