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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Main Authors: Chae Hwa Kwon, Hye Ji Park, Yuri Choi, Yeo Jin Won, Seon Jin Lee, Do Youn Park
Format: Article
Language:English
Published: SAGE Publishing 2017-10-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317722070
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author Chae Hwa Kwon
Hye Ji Park
Yuri Choi
Yeo Jin Won
Seon Jin Lee
Do Youn Park
author_facet Chae Hwa Kwon
Hye Ji Park
Yuri Choi
Yeo Jin Won
Seon Jin Lee
Do Youn Park
author_sort Chae Hwa Kwon
collection DOAJ
description 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.
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publisher SAGE Publishing
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series Tumor Biology
spelling doaj-art-cde3adb50b6a40cda730374e3f665e332025-08-02T19:44:29ZengSAGE PublishingTumor Biology1423-03802017-10-013910.1177/1010428317722070TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cellsChae Hwa KwonHye Ji ParkYuri ChoiYeo Jin WonSeon Jin LeeDo Youn ParkThe 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.https://doi.org/10.1177/1010428317722070
spellingShingle Chae Hwa Kwon
Hye Ji Park
Yuri Choi
Yeo Jin Won
Seon Jin Lee
Do Youn Park
TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
Tumor Biology
title TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
title_full TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
title_fullStr TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
title_full_unstemmed TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
title_short TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells
title_sort twist mediates resistance to paclitaxel by regulating akt and bcl 2 expression in gastric cancer cells
url https://doi.org/10.1177/1010428317722070
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AT yeojinwon twistmediatesresistancetopaclitaxelbyregulatingaktandbcl2expressioningastriccancercells
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