NECTIN-4 increased the 5-FU resistance in colon cancer cells by inducing the PI3K–AKT cascade

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• 作者：Dipon Das ; Shakti Ranjan Satapathy ; Sumit Siddharth…
• 关键词：5 ; Fluorouracil (5 ; FU) ; Colon cancer ; NECTIN ; 4 ; Drug resistance ; AKT/PI3K pathway ; Combination therapy
• 刊名：Cancer Chemotherapy and Pharmacology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：76
• 期：3
• 页码：471-479
• 全文大小：1,172 KB
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• 作者单位：Dipon Das (1)
  Shakti Ranjan Satapathy (1)
  Sumit Siddharth (1)
  Anmada Nayak (1)
  Chanakya Nath Kundu (1)
  
  1. KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, 751024, Orissa, India
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Pharmacology and Toxicology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0843

文摘

Purpose 5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance. Methods Cellular cytotoxicity and expressions of different protein markers in colon cancer cells were measured by MTT assay and Western blotting, respectively. Cell cycle regulation, migration and colony formation ability were measured by FACS, wound-healing assay and clonogenic assay, respectively. Results Increased NECTIN-4 expression was observed in 5-FU-resistant (5-FU-R) and 5-FU-exposed HCT-116 cells. A significant increase in the cell proliferation, migration, colony formation, and resistant to 5-FU were noted in 5-FU-R cells, but reverse was observed after silencing of NECTIN-4. Apoptosis caused by 5-FU in 5-FU-R cells after NECTIN-4 knockdown indicates that NECTIN-4 is responsible for 5-FU resistance. Cell survival proteins were upregulated in 5-FU-R and NECTIN-4-over-expressed cells and downregulated in NECTIN-4 knockdown or LY294002-pretreated 5-FU-R cells. Drug combination of BCNU?+?Resveratrol decreased the cell survival and NECTIN-4 expressions in 5-FU-R cells and NECTIN-4-over-expressed cells. Conclusions Our data suggest that NECTIN-4 is responsible for 5-FU resistance and BCNU?+?Resveratrol combination can be used to increase the 5-FU sensitivity.