| Title of Article |
Repression of Nrf2 enhances antitumor effect of 5-fluorouracil and gemcitabine on cholangiocarcinoma cells |
| Date of Acceptance |
2 February 2015 |
| Journal |
| Title of Journal |
Naunyn-Schmiedeberg's Archives of Pharmacology |
| Standard |
ISI |
| Institute of Journal |
Springer International Publishing AG, Part of Springer Science+Business Media |
| ISBN/ISSN |
0028-1298 |
| Volume |
2558 |
| Issue |
388 |
| Month |
กุมภาพันธ์ |
| Year of Publication |
2015 |
| Page |
601-612 |
| Abstract |
Resistance to chemotherapy is the major problem
in cancer treatment. Cholangiocarcinoma (CCA) is
the tumor arising from the bile duct epithelium. The
disease is characterized by very poor prognosis and
rarely responds to current radiotherapy or chemotherapy.
Transcription factor Nrf2 is activated by oxidative stress
and electrophiles and contributes to cytoprotection in
normal cells as well as cancer cells. Inhibition of Nrf2
can enhance the sensitivity of cancer cells to chemotherapeutic
agents, although this sensitizing effect is variable
depending on the cancers. In this study, we selected
three CCA cell lines with different Nrf2 expression
levels, detected by immunocytofluorescent staining.
Chemotherapeutic agents variably induced the expression
of antioxidant and xenobiotic metabolizing genes
including Nrf2, NQO1, HO-1, GCLC, and GSTP1.
Knockdown of Nrf2 expression by siRNA suppressed
protein expression of Nrf2-regulated genes and enhanced
the sensitivity to 5-fluorouracil and gemcitabine
of CCA cells in both high and low basal Nrf2 expression.
Cells with more resistance to chemotherapeutic
agents gained more chemosensitizing effect by Nrf2 inhibition
than the sensitive cells. The IC50 of the chemotherapeutic
agents was also significantly reduced and
the maximal cytotoxic effect was increased. Suppression
of Nrf2 signaling may be a strategy to increase the
efficacy of chemotherapy to CCA. |
| Keyword |
Nrf2 . Cholangiocarcinoma . Chemosensitizing . Chemotherapeutic agents . Antioxidant . Drug-metabolizing enzyme |
| Author |
|
| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ตีพิมพ์แล้ว |
| Level of Publication |
นานาชาติ |
| citation |
false |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Publication
Journal Publication
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