Radiosensitization of human pancreatic cancer by piperlongumine analogues |
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Authors: | Hao Ma Yuelin Wu Wannian Zhang Huojun Zhang Zhenyuan Miao Chunlin Zhuang |
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Institution: | 1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China;2. Department of Radiation Oncology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China;3. School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China;4. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China;5. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China |
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Abstract: | Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS) expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer. |
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Keywords: | Piperlongumine Pancreatic cancer Radiosensitization Sensitivity enhancement ratio (SER) Reactive oxygen species (ROS) Keap1-Nrf2 Bi-flank xenograft tumor model |
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