|
|
Publication
|
| Research Title |
Nrf2 silencing confers chemosensitizing effect on cholangiocarcinoma cells via repression of antioxidant genes and induction of cell cycle arrest |
| Date of Distribution |
3 February 2016 |
| Conference |
| Title of the Conference |
The 13th Asia Pacific Federation of Pharmacologist (APFP) Meeting |
| Organiser |
The Pharmacological and Therapeutic Society of Thailand, The Asia Pacific Federation of Pharmacologists |
| Conference Place |
The Berkeley Hotel Pratunam |
| Province/State |
Bangkok, Thailand |
| Conference Date |
1 February 2016 |
| To |
3 February 2016 |
| Proceeding Paper |
| Volume |
2559 |
| Issue |
13 |
| Page |
98 |
| Editors/edition/publisher |
APFP 2016 |
| Abstract |
The nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor which plays important role in cellular protection from various toxic and carcinogenic agents. Induction of Nrf2 in cancer cells provides chemoresistance by upregulation of the expression of a number of antioxidant genes and thereby, rendering cancer resistance and growth. Cholangiocarcinoma (CCA) is a very aggressive and resistance malignancy and is a major health problem in Thailand. The aim of study was to determine the effect of Nrf2 inhibition on the sensitivity to chemotherapy in cancer cells. CCA cell lines, KKU-M156, KKU-M214, KKU-M213 and KKU-100 were used in the study. Nrf2 expression was suppressed by siRNA and sensitivity to anticancer drugs, gemcitabine (Gem), cisplatin (Cis) and 5-fluorouracil (5-FU) was analyzed by acridine-orange/ethidium bromide. The result was found that the cytotoxicity in Nrf2-knockdown cells was highly enhanced. The exposure to Gem, Cis, 5-FU, and tBHQ, a potent Nrf2 inducer, induced mRNA expression of Nrf2 and antioxidant genes, including NQO1, HO-1, GCLC, and GSTP1 and expression of protein NQO1, HO-1, GCLC, and Trx in KKU-100 and KKU-M156 cells. Knockdown of Nrf2 suppressed the Cis-induced expression of Nrf2 and Nrf2-regulated genes. In flow cytometric analysis, inhibition of Nrf2 in KKU-M156 altered cell cycle progression by blocking the G0/G1 to S transition. Treatment with Cis induced DNA damage and caused an increase of cells at the S phase. Nrf2 knockdown cells treated with Cis resulted cells accumulated in the G0/G1phase. Suppression of Nrf2 signaling confers chemosensitizing effect on cholangiocarcinoma cells via repression of antioxidant genes and induction cell cycle arrest. Targeting on Nrf2 may be a novel strategy in improve efficacy in chemotherapy of CCA. This work was supported by the Office of the Higher Education Commission through the Health Cluster, SHeP-GMS of Khon Kaen University, Grants in-aid from Khon Kaen University and a scholarship from the Royal Golden Jubilee Ph.D. Programme. |
| Author |
|
| Peer Review Status |
มีผู้ประเมินอิสระ |
| Level of Conference |
นานาชาติ |
| Type of Proceeding |
Abstract |
| Type of Presentation |
Poster |
| Part of thesis |
true |
| Presentation awarding |
true |
| Award Title |
The Best Poster Presentation Award |
| Type of award |
รางวัลด้านวิชาการ วิชาชีพ |
| Organiser |
The Pharmacological and Therapeutic Society of Thailand, The Asia Pacific Federation of Pharmacologists |
| Date of awarding |
3 กุมภาพันธ์ 2559 |
| Attach file |
|
| Citation |
0
|
|
|
|
|
|
|
|
|
Journal Publication
ไทย