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Cancer Chemotherapy and Pharmacology

Published in:

01-09-2015 | Original Article

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

Authors: Dipon Das, Shakti Ranjan Satapathy, Sumit Siddharth, Anmada Nayak, Chanakya Nath Kundu

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2015

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.

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Title: NECTIN-4 increased the 5-FU resistance in colon cancer cells by inducing the PI3K–AKT cascade
Authors: Dipon Das
Shakti Ranjan Satapathy
Sumit Siddharth
Anmada Nayak
Chanakya Nath Kundu
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2794-8

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Abstract

Purpose

Methods

Results

Conclusions

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