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Supplementary figure S2 from Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non–Small Cell Lung Cancer

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posted on 2023-04-03, 15:43 authored by Jianguo Feng, Shirong Zhang, Kan Wu, Bing Wang, Jeffrey Y.C. Wong, Hong Jiang, Rujun Xu, Lisha Ying, Haixiu Huang, Xiaoliang Zheng, Xufeng Chen, Shenglin Ma

Effects of SAHA and Cisplatin on IR-induced DNA damage repair in human lung cancer cells

Funding

National Nature and Science Foundation of China

Zhejiang Provincial Foundation of National Science

Natural Science Foundation of Zhejiang Province, China

Zhejiang Provincial Medicine and Health Science Foundation, China

Zhejiang Medical Science Foundation, China

Hangzhou Key Disease and Discipline Foundation, China

Major Science and Technology Innovation Project of Hangzhou

Medical and Scientific Research Projects of Hangzhou, China

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ARTICLE ABSTRACT

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.

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    Molecular Cancer Therapeutics

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    Biological Agents & TherapiesGene therapyChemotherapyCombination chemotherapyDrug MechanismsModulation of DNA repairLung CancerRadiation OncologyCombined modality therapiesExperimental radiotherapeuticsModification of radiation sensitivityRadioprotectors and radiosensitizersSmall Molecule AgentsPlatinum complexesStem Cell Biology

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