Cancer Chemotherapy and Pharmacology

, Volume 76, Issue 3, pp 471–479 | Cite as

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

  • Dipon Das
  • Shakti Ranjan Satapathy
  • Sumit Siddharth
  • Anmada Nayak
  • Chanakya Nath Kundu
Original Article

Abstract

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.

Keywords

5-Fluorouracil (5-FU) Colon cancer NECTIN-4 Drug resistance AKT/PI3K pathway Combination therapy 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Dipon Das
    • 1
  • Shakti Ranjan Satapathy
    • 1
  • Sumit Siddharth
    • 1
  • Anmada Nayak
    • 1
  • Chanakya Nath Kundu
    • 1
  1. 1.KIIT School of BiotechnologyKIIT UniversityBhubaneswarIndia

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