Open Access

Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines

  • Authors:
    • Somphon Roeksomtawin
    • Panida Navasumrit
    • Somchamai Waraprasit
    • Varabhorn Parnlob
    • Thaniya Sricharunrat
    • Vajarabhongsa Bhudhisawasdi
    • Niramol Savaraj
    • Mathuros Ruchirawat
  • View Affiliations

  • Published online on: May 24, 2018     https://doi.org/10.3892/ol.2018.8807
  • Pages: 1529-1538
  • Copyright: © Roeksomtawin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cholangiocarcinoma (CCA) is a severe cancer with poor prognosis. The aim of the present study was to explore the expression of argininosuccinate synthetase (ASS), as well as the possibility of using pegylated arginine deiminase (ADI‑PEG20) for the treatment of CCA. ASS expression was determined in CCA specimens from 40 patients in Thailand. Immunohistochemical detection of ASS and determination of the proliferative index, Ki‑67, were carried out in paraffin‑embedded sections of these specimens, as well as in two CCA cell lines, HuCCA and RmCCA‑1, derived from CCA samples from patients in Thailand. In total, ~45% of the CCA specimens had low ASS expression, and the level of expression was significantly negatively associated with cell differentiation (P<0.05) and Ki‑67 expression (P<0.05). The level of ASS expression in tumor cells was significantly lower than that in non‑tumor cells (1.3‑fold, P<0.05). The HuCCA cell line had significantly lower levels (P<0.05) of ASS expression at the mRNA and protein levels relative to those of normal human immortalized fibroblast cells (BJ‑1). By contrast, the RmCCA‑1 cell line showed no significant difference. In addition, the effects of ADI‑PEG20 on growth inhibition, apoptosis and cell cycle arrest were determined in HuCCA and RmCCA‑1 cells. ADI‑PEG20 treatment reduced cell viability and cell proliferation in the two CCA cell lines, though it had no effect in immortalized BJ‑1 cells. Furthermore, ADI‑PEG20 treatment significantly increased G0/G1 cell cycle arrest in HuCCA, though not in RmCCA‑1 cells. ASS silencing in the RmCCA‑1 cell line significantly enhanced its sensitivity to ADI‑PEG20 treatment. Results from the in vitro study demonstrated that ADI‑PEG20 has antitumor activity against CCA with low ASS expression.
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August-2018
Volume 16 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Roeksomtawin S, Navasumrit P, Waraprasit S, Parnlob V, Sricharunrat T, Bhudhisawasdi V, Savaraj N and Ruchirawat M: Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines. Oncol Lett 16: 1529-1538, 2018.
APA
Roeksomtawin, S., Navasumrit, P., Waraprasit, S., Parnlob, V., Sricharunrat, T., Bhudhisawasdi, V. ... Ruchirawat, M. (2018). Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines. Oncology Letters, 16, 1529-1538. https://doi.org/10.3892/ol.2018.8807
MLA
Roeksomtawin, S., Navasumrit, P., Waraprasit, S., Parnlob, V., Sricharunrat, T., Bhudhisawasdi, V., Savaraj, N., Ruchirawat, M."Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines". Oncology Letters 16.2 (2018): 1529-1538.
Chicago
Roeksomtawin, S., Navasumrit, P., Waraprasit, S., Parnlob, V., Sricharunrat, T., Bhudhisawasdi, V., Savaraj, N., Ruchirawat, M."Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines". Oncology Letters 16, no. 2 (2018): 1529-1538. https://doi.org/10.3892/ol.2018.8807