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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Format: | Article |
Language: | English |
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SAGE Publishing
2017-10-01
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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. |
format | Article |
id | doaj-art-cde3adb50b6a40cda730374e3f665e33 |
institution | Matheson Library |
issn | 1423-0380 |
language | English |
publishDate | 2017-10-01 |
publisher | SAGE Publishing |
record_format | Article |
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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