Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines
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Updated: Jun 28, 2026
Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Tsutomu Iwasa1, Isamu Okamoto, Minoru Suzuki
1Department of Medical Oncology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Purpose:
Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effect of YM155, a small-molecule inhibitor of survivin expression, on the sensitivity of human non-small cell lung cancer (NSCLC) cell lines to gamma-radiation.
Experimental Design:
The radiosensitizing effect of YM155 was evaluated on the basis of cell death, clonogenic survival, and progression of tumor xenografts. Radiation-induced DNA damage was evaluated on the basis of histone H2AX phosphorylation and foci formation.
Results:
YM155 induced down-regulation of survivin expression in NSCLC cells in a concentration- and time-dependent manner. A clonogenic survival assay revealed that YM155 increased the sensitivity of NSCLC cells to gamma-radiation in vitro. The combination of YM155 and gamma-radiation induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Immunofluorescence analysis of histone gamma-H2AX also showed that YM155 delayed the repair of radiation-induced double-strand breaks in nuclear DNA. Finally, combination therapy with YM155 and gamma-radiation delayed the growth of NSCLC tumor xenografts in nude mice to a greater extent than did either treatment modality alone.
Conclusions:
These results suggest that YM155 sensitizes NSCLC cells to radiation both in vitro and in vivo, and that this effect of YM155 is likely attributable, at least in part, to the inhibition of DNA repair and enhancement of apoptosis that result from the down-regulation of survivin expression. Combined treatment with YM155 and radiation warrants investigation in clinical trials as a potential anticancer strategy.
Insights
YM155 enhances radiation therapy for non-small cell lung cancer (NSCLC) by inhibiting survivin, increasing apoptosis, and delaying DNA repair. This combination therapy shows promise for treating NSCLC tumors in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Survivin, an inhibitor of apoptosis protein, is a key target in cancer therapy.
- Non-small cell lung cancer (NSCLC) presents challenges in treatment, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the radiosensitizing effect of YM155, a survivin inhibitor, on human NSCLC cell lines.
- To evaluate the impact of YM155 on radiation-induced DNA damage and repair.
Main Methods:
- Assessed YM155's effect on cell death, clonogenic survival, and tumor xenograft progression.
- Measured radiation-induced DNA damage via histone H2AX phosphorylation and foci formation.
- Analyzed survivin expression, apoptosis, and caspase-3 activity.
Main Results:
- YM155 down-regulated survivin expression in NSCLC cells.
- YM155 increased NSCLC cell sensitivity to gamma-radiation in vitro.
- Combination therapy synergistically increased apoptosis and delayed DNA repair.
- Combined YM155 and radiation therapy significantly inhibited NSCLC tumor xenograft growth in vivo.
Conclusions:
- YM155 sensitizes NSCLC cells to radiation, likely by inhibiting DNA repair and enhancing apoptosis via survivin down-regulation.
- Combined YM155 and radiation therapy demonstrates potential as an anticancer strategy for NSCLC.
- Further clinical trials are warranted to explore this combined treatment approach.
