title: Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer.
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.
authors.affiliation: Cancer Research Institute and Key Laboratory Diagnoses and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China. Affiliated Hangzhou First People's Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Shirong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Affiliated Hangzhou First People's Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wu
authors.affiliation: Affiliated Hangzhou First People's Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, City of Hope Cancer Center, Duarte, California.
authors.forename: Jeffrey Y C
authors.initials: JY
authors.lastname: Wong
authors.affiliation: Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China.
authors.forename: Rujun
authors.initials: R
authors.lastname: Xu
authors.affiliation: Cancer Research Institute and Key Laboratory Diagnoses and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Ying
authors.affiliation: Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Huang
authors.affiliation: Centre of Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China. Affiliated Hangzhou First People's Hospital of Zhejiang Chinese Medical University, Hangzhou, China. mashenglin@medmail.com.cn.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D011836:Radiation Tolerance / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D006877:Hydroxamic Acids; D000077337:Vorinostat; D002945:Cisplatin