Radiosensitizing Effect of YM155, a Novel Small-Molecule Survivin Suppressant, in Non–Small Cell Lung Cancer Cell Lines

• DOI: 10.1158/1078-0432.ccr-08-0468
• Publication Date: 2008-10-16T18:33:49Z
• Authors: Tsutomu Iwasa; Isamu Okamoto; Minoru Suzuki; Takahito Nakahara; Kentaro Yamanaka; Erina Hatashita; Yuki Yamada; Masahiro Fukuoka; Koji Ono; Kazuhiko Nakagawa
• Keywords: Survivin; Clonogenic assay

Abstract Purpose: Survivin, a member of the inhibitor apoptosis protein family, is an attractive target for cancer therapy. We have now investigated effect YM155, small-molecule survivin expression, on sensitivity human non–small cell lung (NSCLC) lines to γ-radiation. Experimental Design: The radiosensitizing YM155 was evaluated basis death, clonogenic survival, and progression tumor xenografts. Radiation-induced DNA damage histone H2AX phosphorylation foci formation. Results: induced down-regulation expression in NSCLC cells concentration- time-dependent manner. A survival assay revealed that increased γ-radiation vitro. combination synergistic increases both number apoptotic activity caspase-3. Immunofluorescence analysis γ-H2AX also showed delayed repair radiation-induced double-strand breaks nuclear DNA. Finally, therapy with growth xenografts nude mice greater extent than did either treatment modality alone. Conclusions: These results suggest sensitizes radiation vitro vivo, this likely attributable, at least part, inhibition enhancement result from expression. Combined warrants investigation clinical trials as potential anticancer strategy.