Open Access

ARTICLE

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/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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