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Inhibition of NF-kB Activity Enhances Sensitivity to Anticancer Drugs in Cholangiocarcinoma Cells

Wunchana Seubwai*†‡, Kulthida Vaeteewoottacharn‡§, Ratthaphol Kraiklang, Kazuo Umezawa#, Seiji Okada**, Sopit Wongkham‡§

* Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
† Comprehensive Cancer Research Group, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
‡ Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
§ Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
¶ Department of Nutrition, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
# Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Japan
** Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Honjo, Kumamoto, Japan

Oncology Research 2015, 23(1-2), 21-28. https://doi.org/10.3727/096504015X14424348426071

Abstract

Cholangiocarcinoma (CCA) is a dismal cancer. At present, there is no effective chemotherapeutic regimen for CCA. This may be due to the marked resistance of CCA to chemotherapy drugs, for which a mechanism remains unknown. Nuclear factor-kB (NF-kB) is constitutively activated in a variety of cancer cells, including CCA. It has been shown to play roles in growth, metastasis, and chemoresistance of cancer. In the present study, we examined whether NF-kB is involved in the chemoresistance of CCA and whether dehydroxymethylepoxyquinomicin (DHMEQ), an effective NF-kB inhibitor, can overcome the drug resistance of CCA. Two CCA cell lines, KKU-M213 and KKU-M214, were treated with DHMEQ and/or chemotherapeutic drugs. Cell viability, apoptosis, and the expressions of the ATP-binding cassette (ABC) transporters were compared. The combination of chemotherapy drugs, 5-fluorouracil, cisplatin, and doxorubicin, with DHMEQ significantly enhanced the cytotoxicity of all chemotherapeutic drugs compared to DHMEQ or drug alone. Furthermore, the mRNA level of ABCB1, a multidrug-resistant protein, was significantly decreased in the 5-fluorouracil combined with DHMEQ-treated cells. These findings suggest that the inhibition of NF-kB by DHMEQ enhanced the chemoresponsiveness of CCA cells, possibly by reducing the expression of ABC transporter. Inhibition of NF-kB may be a potential chemodrug-sensitizing strategy for chemoresistant cancer such as CCA.

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APA Style
Seubwai, W., Vaeteewoottacharn, K., Kraiklang, R., Umezawa, K., Okada, S. et al. (2015). Inhibition of nf-kb activity enhances sensitivity to anticancer drugs in cholangiocarcinoma cells. Oncology Research, 23(1-2), 21-28. https://doi.org/10.3727/096504015X14424348426071
Vancouver Style
Seubwai W, Vaeteewoottacharn K, Kraiklang R, Umezawa K, Okada S, Wongkham S. Inhibition of nf-kb activity enhances sensitivity to anticancer drugs in cholangiocarcinoma cells. Oncol Res. 2015;23(1-2):21-28 https://doi.org/10.3727/096504015X14424348426071
IEEE Style
W. Seubwai, K. Vaeteewoottacharn, R. Kraiklang, K. Umezawa, S. Okada, and S. Wongkham, “Inhibition of NF-kB Activity Enhances Sensitivity to Anticancer Drugs in Cholangiocarcinoma Cells,” Oncol. Res., vol. 23, no. 1-2, pp. 21-28, 2015. https://doi.org/10.3727/096504015X14424348426071



cc Copyright © 2015 The Author(s). Published by Tech Science Press.
This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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