Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo

Jeng Long‐Bin; Kumar Velmurugan Bharath; Chen Ming‐ChengHsu Hsi‐HsienHo Tsung‐JungDay Cecilia‐HsuanLin Yueh‐MinPadma V. VijayaTu Chuan‐ChouHuang Chih‐Yang

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Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo

机译：在父母的非瑟酮介导凋亡细胞死亡结直肠和铂/伊立替康的抵抗力肿瘤细胞在体外和体内

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Irinotecan (CPT11) and Oxaliplatin have been used in combination with fluorouracil and leucovorin for treating colorectal cancer. However, the efficacy of these drugs is reduced due to various side effects and drug resistance. Fisetin, a hydroxyflavone possess anti‐proliferative, anti‐cancer, anti‐inflammatory, and antioxidant activity against various types of cancers. Apart from that, fisetin has been shown to induce cytotoxic effects when combined with other known chemotherapeutic drugs. In this study, we aimed to investigate whether Fisetin was capable of sensitizing both Irinotecan and Oxaliplatin resistance colon cancer cells and explored the possible signaling pathways involved using In vitro and In vivo models. The results showed that Fisetin treatment effectively inhibited cell viability and apoptosis of CPT11‐LoVo cells than Oxaliplatin (OR) and parental LoVo cancer cells. Western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase‐8, and Cytochrome‐C expressions possibly by inhibiting aberrant activation of IGF1R and AKT proteins. Furthermore, fisetin inhibited tumor growth in athymic nude mouse xenograft model. Overall, our results provided a basis for Fisetin as a promising agent to treat parental as well as chemoresistance colon cancer.

机译：伊立替康(CPT11)和铂结合氟尿嘧啶和亚叶酸治疗结直肠癌。由于各种这些药物的疗效降低副作用和耐药性。hydroxyflavone具有抗高增生性地理反检测癌症,抗炎症,抗氧化剂活动对各种类型的癌症。,非瑟酮诱导当结合其他已知的细胞毒性效应化疗药物。非瑟酮是否有能力进行调查敏化伊立替康和铂抗结肠癌细胞,探索了使用中可能涉及的信号通路体外和体内模型。非瑟酮治疗有效地抑制细胞可行性和CPT11 lovos应承担的凋亡细胞铂(或)和父母lovos癌细胞。免疫印迹分析表明细胞凋亡非瑟酮引起的管理、推广半胱天冬酶量8,细胞色素C表达式可能通过抑制异常激活IGF1R和一种蛋白激酶的蛋白质。肿瘤生长在无胸腺的裸鼠异种移植模型。把父母当作非瑟酮是一种很有前途的代理以及化学抗性结肠癌。

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来源
《Journal of Cellular Physiology》 |2018年第9期|7134-7142|共9页
作者
Jeng Long‐Bin; Kumar Velmurugan Bharath; Chen Ming‐ChengHsu Hsi‐HsienHo Tsung‐JungDay Cecilia‐HsuanLin Yueh‐MinPadma V. VijayaTu Chuan‐ChouHuang Chih‐Yang;
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Department of Chinese MedicineChina Medical University Beigang HospitalYunlin,Taiwan;

Department of BiotechnologyBharathiar UniversityCoimbatore,India;

Department of Surgery and Organ Transplantation CenterChina Medical University HospitalTaichungGraduate Institute of Basic Medical ScienceChina Medical UniversityTaichung,TaiwanDivision of Colorectal SurgeryMackay Memorial HospitalTaipei,TaiwanDivision of Colorectal SurgeryTaichung Veterans General HospitalTaichung,TaiwanDepartment of PathologyChanghua Christian HospitalChanghua,TaiwanDivision of Chest MedicineArmed Force Taichung General HospitalTaichung,TaiwanToxicology and Biomedicine Research GroupTon Duc Thang UniversityHo Chi Minh City,VietnamDepartment of NursingMeiHo UniversityPingtung,Taiwan;

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正文语种英语
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关键词
Cell Death; irinotecan; cancer cellCancer of ColonIn vivooxaliplatinfisetin;

机译：细胞死亡、伊立替康、癌症cellCancer ColonIn;

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Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo

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