title: The effects of SAHA on radiosensitivity in pancreatic cancer cells by inducing apoptosis and targeting RAD51.
abstract: Suberoyl anilide hydroxamic acid (SAHA) is one of the most promising Histone deacetylases(HDAC) inhibitors which has shown significant anti-tumor activity for many malignancies. We explored the potential mechanism of the radiosensitivity effect of SAHA in Panc-1 cells and attempted to develop SAHA as a systemic treatment strategy for pancreatic cancer. Growth inhibition was detected by CCK-8 assay. Radiosensitizing enhancement ratio was determined by clonogenic assay. The cell cycle and apoptosis assay was detected using flow cytometry and annexin-V/PI. The level of Bax, Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression were detected using Western blot analysis. Gene silencing was processed by lentiviral vector and qRT-PCR was performed to detect mRNA expression. The results revealed that SAHA inhibited the proliferation of Panc-1 cells. SAHA enhanced the radiosensitivity with a sensitization enhancement ratio(SER) of 1.10 of the Panc-1 cells. SAHA induced G2-M phase arrest and apoptosis of Panc-1 cells with radiation. SAHA upregulated Bax and downregulated Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression of irradiated Panc-1 cells. SAHA enhanced the radiosensitivity of Panc-1 cells by modulating RAD51 expression. SAHA enhanced radiosensitivity to pancreatic carcinoma Panc-1 cells. It was associated with the G2-M phase arrest and apoptosis via modulation of Bax and Bcl-2 expression. Downregulation of Ku70, Ku86, RAD51 and RAD54 expression caused suppression of HR-mediated DNA repair. SAHA is a good radiosensitizer for pancreatic cancer treatment.
authors.affiliation: Center of Hyperthermia Oncology, Nanjing Medical University Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou, Zhejiang 310006, China; Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China; Key Laboratory of molecular oncology of Chinese medicine and Western medicine, Hangzhou, Zhejiang 310006, China. Electronic address: wu_zhibing@163.com.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Oncology, Cixi People's Hospital, Cixi, Zhejiang 315300, China.
authors.forename: Saisai
authors.initials: S
authors.lastname: Jing
authors.affiliation: Department of Oncology, Cixi People's Hospital, Cixi, Zhejiang 315300, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Center of Hyperthermia Oncology, Nanjing Medical University Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou, Zhejiang 310006, China.
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Center of Hyperthermia Oncology, Nanjing Medical University Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou, Zhejiang 310006, China.
authors.forename: Zhitian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of molecular oncology of Chinese medicine and Western medicine, Hangzhou, Zhejiang 310006, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of molecular oncology of Chinese medicine and Western medicine, Hangzhou, Zhejiang 310006, China.
authors.forename: Jigang
authors.initials: J
authors.lastname: Piao
authors.affiliation: Center of Hyperthermia Oncology, Nanjing Medical University Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou, Zhejiang 310006, China; Key Laboratory of molecular oncology of Chinese medicine and Western medicine, Hangzhou, Zhejiang 310006, China.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D051135:Rad51 Recombinase / Q000187:drug effects*; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D011838:Radiation-Sensitizing Agents; D000077337:Vorinostat; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: Apoptosis; Pancreatic cancer; RAD51; Radiosensitivity