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R. Xu
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-012 - Combined Effects of SAHA and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in NSCLC (ID 538)
09:30 - 17:00 | Author(s): R. Xu
- Abstract
Background:
Lung cancer is a leading cause of cancer mortality worldwide. In an effort to improve local control of the disease and to increase survival, concurrent chemoradiotherapy has been explored as a therapeutic option. Of them, cisplatin-based chemoradiotherapy is currently used as first line therapy for non-small-cell lung cancer (NSCLC). However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and thus further optimizations of chemotherapy regimen to be given with radiation are needed.
Methods:
We examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs using U2OS reporter cells and in vivo end-joining assay, and determined the combination effects of SAHA and cisplatin on various cell lines, primary tumor tissues and in vivo xenograft in response to irradiation. We also investigated the potential differentiation effect of SAHA and its consequent effect on cancer cell invasion in cisplatin-treated cancer cells.
Results:
Our data demonstrated that SAHA and cisplatin compromised distinct DNA damage repair pathways. Treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in NSCLC cells, and induced prolonged persistence of γ-H2A.X nuclear foci in irradiated primary NSCLC tumor tissues treated with cisplatin. SAHA combined with cisplatin also significantly increased inhibitory effect of ionizing radiation on tumor growth in mouse xenograft model. In addition, we showed here that SAHA could induce differentiation in stem cell-like cancer cell population, reduce tumorogenesity and decrease the invasion/migration capabilities of human lung cancer H460 cells.
Conclusion:
Our results suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of chemoradiotherapy regimen for NSCLC. The strategy may also benefit those patients with high risk of cancer metastasis.
