in two CCA cell lines, HuCCA and RmCCAâ1, derived from. CCA samples from ..... determined using a Muse Cell Analyzer (EMD Millipore). Cell cycle analysis.
ONCOLOGY LETTERS
Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI‑PEG20 treatment in CCA cell lines SOMPHON ROEKSOMTAWIN1,2, PANIDA NAVASUMRIT1‑3, SOMCHAMAI WARAPRASIT1, VARABHORN PARNLOB1, THANIYA SRICHARUNRAT4, VAJARABHONGSA BHUDHISAWASDI5,6, NIRAMOL SAVARAJ7 and MATHUROS RUCHIRAWAT1‑3 1
Laboratory of Environmental Toxicology, Chulabhorn Research Institute; 2Chulabhorn Graduate Institute, Bangkok 10210; 3Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, Bangkok 10300; 4Chulabhorn Hospital, Bangkok 10210; 5Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kean 40000; 6Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok 10210, Thailand; 7Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33125, USA Received September 20, 2017; Accepted May 3, 2018 DOI: 10.3892/ol.2018.8807 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 determina‑ tion 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 (P3 sets of data using the Bonferroni test for post hoc analysis. Pearson's correlation was used to assess correlation between proliferation and expression level of ASS or CCA stage. Results Immunohistochemical analysis of ASS expression in CCA specimens and its relationship to clinicopathological parameters. In order to investigate whether CCA may be an arginine auxotrophic cancer, the levels of ASS expres‑ sion in 40 human CCA specimens were determined using immunohistochemistry. Our results showed that the intensity of cytoplasmic ASS staining in cancer cells was much lower than in the surrounding non‑tumor liver cells in specimens from CCA patients (Fig. 1A‑C). The level of ASS expres‑ sion, quantified as the relative intensity of ASS staining, is summarized in Table I. In CCA, the mean intensity of ASS staining in tumor cells was 1.3‑fold lower than for non‑tumor cells (33.56 vs. 44.23, P
