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Authors Yang K, Gao K, Hu G, Wen Y, Lin C, Li X
Received 21 March 2016
Accepted for publication 7 August 2016
Published 30 November 2016 Volume 2016:9 Pages 7285—7295
DOI https://doi.org/10.2147/OTT.S108929
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Jia Fan
Peer reviewer comments 3
Editor who approved publication: Professor Min Li
Abstract: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers
among both males and females; the chemotherapy drug 5-fluorouracil (5-FU) is
one of a doctors’ first lines of defense against CRC. However, therapeutic
failures are common because of the emergence of drug resistance. Connective
tissue growth factor (CTGF) is a secreted protein that binds to integrins, and
regulates the invasiveness and metastasis of certain carcinoma cells. Here, we
found that CTGF was upregulated in drug-resistant phenotype of human CRC cells.
Overexpression of CTGF enhanced the resistance to 5-FU-induced cell apoptosis.
Moreover, downregulating the expression of CTGF promoted the curative effect of
chemotherapy and blocked the cell cycle in the G1 phase. We also found that
CTGF facilitated resistance to 5-FU-induced apoptosis by increasing the
expression of B-cell lymphoma-extra large (Bcl-xL) and survivin. Then we
pharmacologically blocked MEK/ERK signal pathway and assessed 5-FU response by
MTT assays. Our current results indicate that the expression of phosphorylated
forms of MEK/ERK increased in high CTGF expression cells and MEK inhibited
increases in 5-FU-mediated apoptosis of resistant CRC cells. Therefore, our
data suggest that MEK/ERK signaling contributes to 5-FU resistance through
upstream of CTGF, and supports CRC cell growth. Comprehending the molecular
mechanism underlying 5-FU resistance may ultimately aid the fight against CRC.
Keywords: connective tissue growth factor,
5-fluorouracil, mitogen-activated protein kinase/extracellular regulated
protein kinases, phosphatidyl inositol 3-kinase/serine/threonine kinase Akt,
colorectal cancer