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Open AccessArticle

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

1
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
2
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
3
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
4
Faculty of Pharmacy, Mahasarakham University, Maha Sarakham 44150, Thailand
*
Author to whom correspondence should be addressed.
Medicina 2019, 55(12), 761; https://doi.org/10.3390/medicina55120761
Received: 3 November 2019 / Revised: 22 November 2019 / Accepted: 24 November 2019 / Published: 28 November 2019
(This article belongs to the Section Hepatology)
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. View Full-Text
Keywords: cancer; chemotherapy; glycosylation; lectin; sialylation cancer; chemotherapy; glycosylation; lectin; sialylation
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Wattanavises, S.; Silsirivanit, A.; Sawanyawisuth, K.; Cha’on, U.; Waraasawapati, S.; Saentaweesuk, W.; Luang, S.; Chalermwat, C.; Wongkham, C.; Wongkham, S. Increase of MAL-II Binding Alpha2,3-Sialylated Glycan Is Associated with 5-FU Resistance and Short Survival of Cholangiocarcinoma Patients. Medicina 2019, 55, 761.

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