title: Synergistic effect of survivin-specific small interfering RNA and topotecan in renal cancer cells: topotecan enhances liposome-mediated transfection by increasing cellular uptake.
abstract: Survivin, an inhibitor of apoptosis (IAP) protein detected in many tumors but not in most normal differentiated tissues, has been widely recognized as an attractive target for cancer therapy. We previously showed that survivin expression is associated with cell proliferation. Although liposome-mediated transfection of survivin-specific siRNA decreases survivin expression and cell proliferation, these effects are limited in part by the low efficiency of the transfection. In the present study we therefore investigated the possibility of better suppressing survivin expression and cell growth by using treatments combining survivin-specific siRNA and the topoisomerase I inhibitor topotecan. Survivin-specific siRNA and topotecan given simultaneously inhibited survivin expression and cell proliferation synergistically, but topotecan alone or topotecan and siRNA given metachronously did not alter survivin expression. We hypothesized that topotecan increases the efficiency of siRNA transfection by increasing cellular uptake, and we confirmed this hypothesis by using fluorescein-labeled siRNA. Combination therapy using survivin-specific siRNA and topotecan should thus show a synergistic effect due to increased cellular uptake of siRNA and offer an attractive approach for treatment of advanced renal cancer.
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. zenpaku@ndmc.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Makoto
authors.initials: M
authors.lastname: Sumitomo
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000378:metabolism*; D000077022:Survivin; D019772:Topotecan / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D019772:Topotecan