| Research Title |
Inhibition of Nrf2 signaling sensitizes cholangiocarcinoma cells to cisplatin in association with cellular oxidative stress
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| Date of Distribution |
29 December 2015 |
| Conference |
| Title of the Conference |
Advanced Oxidative Stress Research for Health Benefits and Well beings |
| Organiser |
Society for Free Radical Research – Asia (SFRR-Asia 2015) |
| Conference Place |
The empress hotel |
| Province/State |
Chiang mai, Thailand |
| Conference Date |
29 November 2015 |
| To |
2 December 2015 |
| Proceeding Paper |
| Volume |
2558 |
| Issue |
1 |
| Page |
65 |
| Editors/edition/publisher |
SFRR-Thai |
| Abstract |
Introduction: Drug resistance is the main obstacle to cancer chemotherapy. Cancer of the bile duct (cholangiocarcinoma:CCA) is the devastating malignancy, as it is poorly response to chemotherapy. The nuclear factor erythroid 2-like 2 (Nrf2) is activated by oxidative stress and contributes to cytoprotection in cancer cells. The association of oxidant stress by Nrf2 inhibition and chemosensitizing effect to cisplatin in CCA cells was investigated.
Materials and methods: CCA cell lines were analyzed for the expression of Nrf2. The Nrf2 expression was suppressed by siRNA and antioxidant gene expression was analyzed by reverse-transcription PCR and Western blotting. The cytotoxicity was assayed by acridine-orange/ethidium bromide and sulforhodamine-B assays.
Results and discussion: KKU-100 and M156 cells with high and low Nrf2 expression were employed to examine the effect of Nrf2 silencing. Knockdown of Nrf2 enhanced the cytotoxicity to cisplatin in both cell lines by 3-6 fold and independence of basal Nrf2 expression. Suppression of Nrf2 resulted in suppression of cisplatin-induced antioxidant gene expression, Nrf2, GCLC and HO-1. Oxidant formation in Nrf2 knockdown cells was implicated in the chemosensitizing effect, as the effect was largely abolished by treatment with superoxide scavenger, Tempol or redox modifier, N-acetylcysteine. Inhibition of Nrf2 signaling could be a novel target to enhance the sensitivity to chemotherapy in CCA.
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| Author |
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| Peer Review Status |
มีผู้ประเมินอิสระ |
| Level of Conference |
นานาชาติ |
| Type of Proceeding |
Abstract |
| Type of Presentation |
Poster |
| Part of thesis |
true |
| ใช้สำหรับสำเร็จการศึกษา |
ไม่เป็น |
| Presentation awarding |
true |
| Award Title |
Young Investigator Award |
| Type of award |
รางวัลด้านวิชาการ วิชาชีพ |
| Organiser |
SFRR-Thai |
| Date of awarding |
2 ธันวาคม 2558 |
| Attach file |
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| Citation |
0
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Publication
Journal Publication
ไทย