title: Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells.
abstract: Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer.
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: yjzhang111@aliyun.com.
authors.forename: Ying-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: liyingyi@fudan.edu.cn.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Li
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing
chemical_list: D011518:Proto-Oncogene Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Cell cycle; DNA damage repair; Pancreatic cancer; Pim-3; Radioresistance