| Research Title |
Knockdown of Nrf2 - Mediated Antioxidant Defense System by siRNA Sensitizes Cholangiocarcinoma Cells to Cisplatin |
| Date of Distribution |
27 March 2014 |
| Conference |
| Title of the Conference |
การประชุมวิชาการสมาคมเภสัชวิทยาแห่งประเทศไทย ครั้งที่ 36 "Advanced Pharmacology in Drug Development: Towards The ASEAN Union" |
| Organiser |
คณะแพทยศาสตร์ศิริราชพยาบาล มหาวิทยาลัยมหิดล |
| Conference Place |
คณะแพทยศาสตร์ศิริราชพยาบาล มหาวิทยาลัยมหิดล |
| Province/State |
กรุงเทพมหานคร |
| Conference Date |
27 March 2014 |
| To |
28 March 2014 |
| Proceeding Paper |
| Volume |
2014 |
| Issue |
36 |
| Page |
25 |
| Editors/edition/publisher |
|
| Abstract |
Nrf2 is a key transcription factor regulated antioxidant enzymes which are contributed to cytoprotection against oxidative stress and electrophilic attack in normal cells as well as cancer cells. Activation of Nrf2 signaling system plays an important role in resistance to chemotherapeutic drugs of many different cancers. Recent evidence suggests that high expression of Nrf2 and antioxidant enzymes in human cancer tissues and cancer cell lines correlates with cells survival and contributes to chemoresistance. Moreover, inhibition of Nrf2 expression increased sensitivity to chemotherapeutic drugs. The present study was to determine whether knockdown of Nrf2 by small interfering RNA (Nrf2-siRNA) in cholangiocarcinoma cells enhances the efficacy of chemotherapy. Human cholangiocarcinoma cells (CCA cells), KKU-M156 were transfected with Nrf2 siRNA for 24 and 48 h to evaluate the efficiency of the target knockdown by RT-PCR. The sensitivity of CCA cells to gemcitabine and cisplatin was determined. Our data show that siRNA-mediated significantly decreased the Nrf2 expression in KKU-M156 cells. The Nrf2 knockdown increased the cytotoxicity of cisplatin, resulting in increased cell death in a dose-dependent manner when compared to the non-target siRNA transfection. Combination of Nrf2 gene silencing with cisplatin caused a significant downregulation of the Nrf2 downstream antioxidant genes including NQO1, HO-1, GCLC and GSTP1. The downregulation of Nrf2 and its downstream genes is associated with potentiation of the efficacy of cisplatin. Suppression of Nrf2 signaling may be a strategy to increase efficacy of chemotherapy.
Keywords: Nrf2, Cholangiocarcinoma, Chemosensitivity, Cisplatin, Antioxidant enzyme
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| Author |
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| Peer Review Status |
มีผู้ประเมินอิสระ |
| Level of Conference |
ชาติ |
| Type of Proceeding |
Abstract |
| Type of Presentation |
Poster |
| Part of thesis |
true |
| Presentation awarding |
false |
| Attach file |
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| Citation |
0
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Publication
Journal Publication
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