TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells

The transcription factor TWIST has been reported to play an important role in tumor progression as well as resistance to anti-cancer drugs. However, the role of TWIST in gastric cancer and the molecular mechanisms by which this protein elicits drug resistance remain poorly understood. We transfected...

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Published inTumor biology Vol. 39; no. 10; p. 101042831772207
Main Authors Kwon, Chae Hwa, Park, Hye Ji, Choi, Yuri, Won, Yeo Jin, Lee, Seon Jin, Park, Do Youn
Format Journal Article
LanguageEnglish
Published London, England SAGE Publications 01.10.2017
Sage Publications Ltd
IOS Press
Subjects
AKT protein
Apoptosis
Bcl-2 protein
Biotechnology
Breast cancer
Cancer therapies
Cell cycle
Cell death
Cell migration
Drug resistance
Gastric cancer
Gene expression
Medical prognosis
Metastasis
Molecular modelling
Ovarian cancer
Paclitaxel
Phosphorylation
siRNA
Stem cells
Transcription factors
Tumor cell lines
United States > US
Bcl-2
paclitaxel
Akt
gastric cancer
TWIST
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Summary:The transcription factor TWIST has been reported to play an important role in tumor progression as well as resistance to anti-cancer drugs. However, the role of TWIST in gastric cancer and the molecular mechanisms by which this protein elicits drug resistance remain poorly understood. We transfected gastric cancer cell lines with lentiviral vector to generate TWIST-overexpressing stable cell lines. Our study showed that overexpression of TWIST not only increased cell migration and invasion but also induced resistance to the anti-cancer drug paclitaxel in gastric cancer. Paclitaxel increased gastric cancer cell death in dose-dependent manner; this was decreased following TWIST overexpression. Furthermore, treatment with paclitaxel decreased Akt phosphorylation and Bcl-2 expression, whereas these effects were suppressed by TWIST overexpression. Treatment of cells with Akt inhibitor or small interfering RNA targeting for Bcl-2 led to increased paclitaxel-induced cell death, indicating that TWIST elicits resistance to paclitaxel via the regulation of the Akt and Bcl-2 pathway. Our results suggest an underlying mechanism for TWIST-mediated paclitaxel resistance and indicate that TWIST represents a potential target for overcoming paclitaxel resistance in gastric cancer cells.
ISSN:1010-4283
1423-0380
DOI:10.1177/1010428317722070