BET inhibitor bromosporine enhances 5-FU effect in colorectal cancer cells |
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| Affiliation: | 1. Department of General Surgery, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai People’s Hospital, Beihai, 536000, Guangxi Zhuang, China;2. Department of General Surgery, Wuming Hospital of Guangxi Medical University, Nanning, 530199, Guangxi Zhuang, China;1. Department of Gastroenterology, Daqing People’s Hospital (The Fifth Affiliated Hospital of Harbin Medical University), Daqing 163316, China;2. Department of Anesthesia, Daqing Longnan Hospital, Daqing 163453, China;3. Department of Ophthalmology, Daqing People’s Hospital (The Fifth Affiliated Hospital of Harbin Medical University), Daqing 163316, China;4. Department of Hematology, Daqing Oilfield General Hospital, Daqing 163000, China;5. Department of Dermatology, Daqing Longnan Hospital, Daqing 163453, China;6. Department of Oncology, Daqing Longnan Hospital, Daqing 163453, China;1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;2. Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, Henan, China;3. Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, China;4. Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, China;5. Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;1. Pharmaceutical Preparation Section, Sanmen People''s Hospital of Zhejiang Province, Sanmen, 317100, China;2. Department of Laboratory Medicine, Taizhou Enze Medical Center (Group) Enze Hospital, Taizhou, 318050, China;3. Department of Integrated Traditional & Western Medicine, Sanmen Hospital of TCM, Sanmen, 317100, China;4. Central Laboratory, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221100, China;5. Central Laboratory, Sanmen People''s Hospital of Zhejiang Province, Sanmen, 317100, China;6. Department of Gastroenterology, Sanmen People''s Hospital of Zhejiang Province, Sanmen, 317100, China;7. Department of General Surgery, Sanmen People''s Hospital of Zhejiang Province, Sanmen, 317100, China |
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| Abstract: | Treatment of colorectal cancer (CRC) remains a challenge because of the lack of effective early treatment strategies and high incidence of relapse. 5-Fluorouracil (5-FU) is a typical CRC treatment. Bromosporine is an innovative bromodomain and extraterminal domain (BET) inhibitor. We investigated if CRC could be targeted by the combination of 5-FU and bromosporine in a synergistic manner in vivo and in vitro. Our findings shown that the combination treatment inhibits cell viability, formation of colonies, increased apoptosis and cell cycle arrest at G0-G1. In addition, the expression level of BRD4 was high in HCT116 cells exposed to 5-FU that showed lower apoptosis against the parental cells. Moreover, the 5-FU-resistance was reversed significantly by BRD4 knockdown or inhibition. The drug combination showed increased activity against tumor than individual drug exposure in the xenograft model. In conclusion, this work serves as a basic clinical evaluation of 5-FU and bromosporine as an effective therapeutic approach for CRC. |
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| Keywords: | Bromosporine 5-FU CRC BRD4 Drug resistance |
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