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Article

Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells

  • Authors:
    • Nichapavee Nutthasirikul
    • Chariya Hahnvajanawong
    • Anchalee Techasen
    • Temduang Limpaiboon
    • Chanvit Leelayuwat
    • Siri Chau-In
    • Patcharee Jearanaikoon
  • View Affiliations / Copyright

    Affiliations: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
  • Pages: 2153-2164
    |
    Published online on: October 5, 2015
       https://doi.org/10.3892/ijo.2015.3188
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Abstract

Lack of the normal p53 transactivation domain, ∆133p53 isoform exhibits anti-p53 function. Many studies report the correlation between ∆133p53 expression and poor survival in various cancers, including cholangiocarcinoma (CCA), which is a cancer of the bile ducts. CCA almost always results in short survival times. The relevance of ∆133p53 to drug resistance in CCA is not yet well understood. This study aimed to demonstrate the association between ∆133p53 and 5-fluorouracil (5-FU) resistance in CCA. ∆133p53 protein was highly expressed in CCA patients with poor outcome compared to favorable outcome but was not statistically significant. However, a significant correlation was found between normalized ∆133p53 levels and 5-FU resistance which was defined by an ex vivo histoculture drug response assay (P=0.019). Two stable 5-FU-resistant CCA cell lines, KKU-M139R (IC50 38.8 µM) and KKU-M214R (IC50 39.5 µM), were used as a model to evaluate the role of ∆133p53. Increased ∆133p53 was correlated with 5-FU in a dose-dependent manner. The transient knockdown of ∆133p53 expression can restore drug sensitivity in both resistant CCA cells with 11- to 45-fold reduction of IC50 compared to control. Upon ∆133p53 silencing, apoptotic signaling was enhanced by the upregulation of Bax and downregulation of Bcl-2. Additionally, p21 and p27 were upregulated, resulting in cell cycle arrest at G2. Inhibition of colony formation and prolong doubling time were also observed. Our findings demonstrated that chemosensitivity can be modulated via targeting of ∆133p53 suggesting the potential use of ∆133p53 as a candidate for targeting therapy in CCA.
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Copy and paste a formatted citation
Spandidos Publications style
Nutthasirikul N, Hahnvajanawong C, Techasen A, Limpaiboon T, Leelayuwat C, Chau-In S and Jearanaikoon P: Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells. Int J Oncol 47: 2153-2164, 2015.
APA
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., & Jearanaikoon, P. (2015). Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells. International Journal of Oncology, 47, 2153-2164. https://doi.org/10.3892/ijo.2015.3188
MLA
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., Jearanaikoon, P."Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells". International Journal of Oncology 47.6 (2015): 2153-2164.
Chicago
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., Jearanaikoon, P."Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells". International Journal of Oncology 47, no. 6 (2015): 2153-2164. https://doi.org/10.3892/ijo.2015.3188
Copy and paste a formatted citation
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Spandidos Publications style
Nutthasirikul N, Hahnvajanawong C, Techasen A, Limpaiboon T, Leelayuwat C, Chau-In S and Jearanaikoon P: Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells. Int J Oncol 47: 2153-2164, 2015.
APA
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., & Jearanaikoon, P. (2015). Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells. International Journal of Oncology, 47, 2153-2164. https://doi.org/10.3892/ijo.2015.3188
MLA
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., Jearanaikoon, P."Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells". International Journal of Oncology 47.6 (2015): 2153-2164.
Chicago
Nutthasirikul, N., Hahnvajanawong, C., Techasen, A., Limpaiboon, T., Leelayuwat, C., Chau-In, S., Jearanaikoon, P."Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells". International Journal of Oncology 47, no. 6 (2015): 2153-2164. https://doi.org/10.3892/ijo.2015.3188
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