Sorafenib induced alteration of protein glycosylation in hepatocellular carcinoma cells

Liu,Tianhua; Liu,Riqiang; Zhang,Shu; Guo,Kun; Zhang,Qinle; Li,Wei; Liu,Yinkun

doi:10.3892/ol.2017.6177

Sorafenib induced alteration of protein glycosylation in hepatocellular carcinoma cells

Authors:
- Tianhua Liu
- Riqiang Liu
- Shu Zhang
- Kun Guo
- Qinle Zhang
- Wei Li
- Yinkun Liu
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Affiliations: Liver Cancer Institute and Cancer Research Center, Zhongshan Hospital, Institute of Biomedical Science, Fudan University, Shanghai 200032, P.R. China, Department of General Surgery, The People's Hospital in Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
Published online on: May 16, 2017 https://doi.org/10.3892/ol.2017.6177
Pages: 517-524
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sorafenib is a multikinase inhibitor and is effective in treating hepatocellular carcinoma (HCC). However, it remains unknown whether sorafenib induces the alteration of protein glycosylation. The present study treated HCC MHCC97L and MHCC97H cells with a 50% inhibitory concentration of sorafenib. Following this treatment, alteration of protein glycosylation was detected using a lectin microarray. Compared with the controls, the binding capacity of glycoproteins extracted from sorafenib‑treated HCC cells to the lectins Bauhinia purpurea lectin, Dolichos biflorus agglutinin, Euonymus europaeus lectin, Helix aspersa lectin, Helix pomatia lectin, Jacalin, Maclura pomifera lectin and Vicia villosa lectin were enhanced; while, the binding capacities to the lectins Caragana arborescens lectin, Lycopersicon esculentum lectin, Limulus polyphemus lectin, Maackia amurensis lecin I, Phaseolus vulgaris leucoagglutinin, Ricinus communis agglutinin 60, Sambucus nigra lectin and Solanum tuberosum lectin were reduced (spot intensity median/background intensity median ≥2, P<0.05). This difference in glycoprotein binding capacity indicates that cells treated with sorafenib could increase α‑1,3GalNAc/Gal, β‑1,3 Gal, GalNAcα‑Ser/Thr(Tn) and α‑GalNAc structures and decrease GlcNAc, sialic acid, tetra‑antennary complex‑type N‑glycan and β‑1,4Gal structures. These results were additionally confirmed by lectin blotting. Expression levels of signaling molecules including erythroblastosis 26‑1 (Ets‑1), extracellular signal‑related kinases (ERK) and phosphorylated‑ERK were measured by western blotting. There was a reduction in the expression of Ets‑1 and ERK phosphorylation in sorafenib or 1,4‑Diamino‑2,3‑dicyano‑1,4‑bis (2‑aminophenylthio) butadiene treated cells suggesting that sorafenib may reduce the expression levels of Ets‑1 by blocking the Ras/Raf/mitogen activated protein kinase signaling pathway. In the present study, it was clear that sorafenib could inhibit the proliferation of HCC cells and alter protein glycosylation. The findings of this study may lead to providing a novel way of designing new anti‑HCC drugs.

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