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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cancer
2017 ; 8
(17
): 3555-3566
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ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial -
Mesenchymal Transition in Colon Cancer Cells
#MMPMID29151941
Guo C
; Ma J
; Deng G
; Qu Y
; Yin L
; Li Y
; Han Y
; Cai C
; Shen H
; Zeng S
J Cancer
2017[]; 8
(17
): 3555-3566
PMID29151941
show ga
Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical
treatment of colon cancer. However, chemo-resistance is still a barrier to
effective chemotherapy in cases of colon cancer. Accumulated evidence suggests
that the epithelial mesenchymal transition (EMT) may be a critical factor in
chemo-sensitivity. The present study investigated the effects of Zinc finger
E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method:
ZEB1expression and its correlation with clinicopathological characteristics were
analyzed using tumor tissue from an independent cohort consisting of 118 colon
cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of
OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline
of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay
was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch
wound healing and transwell assays were used to determine EMT phenotype of colon
cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine
the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice
xenograft model). Result: ZEB1 expression was significantly increased in colon
tumor tissue, and was correlated with lymph node metastasis and the depth of
invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA
cells exhibited an EMT phenotype characterized by up-regulated expression of
ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin.
Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT
phenotype and enhanced OXA-sensitivity in vitro and in vivo. Conclusion:
HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored
OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the
prevention of OXA-resistance in colon cancer.