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2017 ; 14
(1
): 647-654
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Transforming growth factor-?1 contributes to oxaliplatin resistance in colorectal
cancer via epithelial to mesenchymal transition
#MMPMID28693217
Mao L
; Li Y
; Zhao J
; Li Q
; Yang B
; Wang Y
; Zhu Z
; Sun H
; Zhai Z
Oncol Lett
2017[Jul]; 14
(1
): 647-654
PMID28693217
show ga
Transforming growth factor-?1 (TGF-?1), secreted by main components of tumor
microenvironment, is considered to be closely associated with cancer development
and chemoresistance. The present study aimed to analyze the effects and
mechanisms underlying TGF-?1-induced chemoresistance to oxaliplatin (LOH) in
human colorectal cancer (CRC) cell lines. The cytotoxic effects of LOH subsequent
to TGF-?1 treatment were assessed in three CRC cell lines by MTT assay. In
addition, epithelial to mesenchymal transition (EMT), DNA damage and apoptosis
assays were performed to evaluate the mechanisms of drug resistance in vitro. It
was revealed that an exposure of CRC cells to TGF-?1 induced EMT. This was
followed by a decrease in the levels of DNA damage and LOH-induced apoptotic cell
death at certain TGF-?1 concentrations compared with untreated cells, which was
responsible for LOH resistance. TGF-?1 leads to resistance to LOH in CRC cells,
primarily through EMT. These data not only provide insight into the understanding
of the chemoresistant mechanisms, but also may guide the clinical applications of
reducing EMT to enhance the sensitivity to chemotherapy, by targeting TGF-?1.