Increase of MAL-II Binding Alpha2,3-Sialylated Glycan Is Associated with 5-FU Resistance and Short Survival of Cholangiocarcinoma Patients.

Autor:	Wattanavises S; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand., Silsirivanit A; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand., Sawanyawisuth K; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand., Cha'on U; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Waraasawapati S; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand.; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Saentaweesuk W; Faculty of Pharmacy, Mahasarakham University, Maha Sarakham 44150, Thailand., Luang S; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand., Chalermwat C; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Wongkham C; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand., Wongkham S; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand.
Jazyk:	angličtina
Zdroj:	Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2019 Nov 28; Vol. 55 (12). Date of Electronic Publication: 2019 Nov 28.
DOI:	10.3390/medicina55120761
Abstrakt:	Background and Objectives: Sialylation plays important roles in tumor progression. Our present study aimed to demonstrate the alteration of sialylation and its role in cholangiocarcinoma (CCA). Materials and Methods: The α2,3- and α2,6-sialylation in CCA tissue was analyzed by lectin-histochemistry using Maackia amurensis lectin-II (MAL-II) and Sambucus nigra agglutinin (SNA). CCA cell lines were treated with the pan-sialylation inhibitor 3Fax-peracetyl-Neu5Ac (3F-Sia) followed by proliferation and chemosensitivity assays. Results: MAL-II binding α2,3-Sialylated Glycan (MAL-SG) and SNA binding α2,6-Sialylated Glycan (SNA-SG) were both elevated in CCA compared with hyperplastic/dysplastic (HP/DP) and normal bile ducts (NBD). The positive staining for MAL-SG or SNA-SG were found in 82% (61/74) of the CCA cases. Higher expression of MAL-SG in CCA was associated with shorter survival of the patients. The median survival of patients with high and low MAL-SG were 167 and 308 days, respectively, with overall survival of 233 days, suggesting the involvement of MAL-SG in CCA progression. MAL-SG expression of CCA cell lines was markedly decreased after treatment with 3F-Sia for 48 to 72 h. While proliferation of CCA cells were not affected by 3F-Sia treatment, their susceptibility to 5-fluorouracil (5-FU) was significantly enhanced. These results suggest that sialylation is involved in the development of 5-FU resistance and the sialylation inhibitor 3F-Sia can be used as a chemosensitizer for CCA. Conclusions: Sialylation is critically involved in the development of chemoresistance of CCA, and sialylation inhibitors may be used as a chemosensitizer in CCA treatment.
Databáze:	MEDLINE
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