Lung cancer is a leading cause of
cancer-related mortality worldwide, and
concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the
chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of
suberoylanilide hydroxamic acid (SAHA) and
cisplatin on DNA damage repairs, and determined the combination effects of SAHA and
cisplatin on human
non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on
tumor growth of
lung cancer H460 xenografts receiving
radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on
cancer cell invasion. Our results showed that SAHA and
cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of
cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in
cisplatin-treated primary NSCLC
tumor tissues in response to IR. SAHA combined with
cisplatin also significantly increased inhibitory effect of
radiotherapy on
tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell-like
cancer cell population, reduce tumorigenicity, and decrease invasiveness of human
lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a
chemoradiotherapy regimen for NSCLC. Mol
Cancer Ther; 15(5); 842-53. ©2016 AACR.