Targeting hexokinase II as a possible therapy for cholangiocarcinoma
| Autor: | Sopit Wongkham, Ubonrat Thamrongwaranggoon, Thidarat Boonmars, Chatchai Phoomak, Sakkarn Sangkhamanon, Wunchana Seubwai, Ubon Cha'on |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Indazoles Biophysics Biology Biochemistry Metastasis Cholangiocarcinoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Cricetinae Hexokinase parasitic diseases medicine Animals Cytotoxic T cell Enzyme Inhibitors Molecular Biology Cell growth Opisthorchis fungi Lonidamine Cell Biology medicine.disease Immunohistochemistry 030104 developmental biology Bile Duct Neoplasms chemistry Cell culture Apoptosis 030220 oncology & carcinogenesis Immunology Disease Progression Cancer research Cell Division |
| Zdroj: | Biochemical and Biophysical Research Communications. 484:409-415 |
| ISSN: | 0006-291X |
| Popis: | Overexpression of hexokinase 2 (HKII) has been demonstrated in various cancers. A number of in vitro and in vivo studies in several cancers show the significance of HKII in many cellular processes including proliferation, metastasis and apoptosis. However, the role of HKII in Opisthorchis viverrini (Ov) associated cholangiocarcinoma (CCA) is still unknown. In the present study, the expression and roles of HKII were determined in Ov associated CCA. The expression of HKII was investigated in 82 patients with histologically proven CCAs by immunohistochemistry. HKII was distinctively expressed in CCA tissues. It was rarely expressed in normal bile duct epithelium, but was expressed in hyperplastic/dysplastic and in 82% of CCA bile ducts. The observation was confirmed in the Ov associated hamster model. Suppression of HKII expression using siRNA significantly decreased cell proliferation, migration and invasion of CCA cell lines. Similar results were obtained using lonidamine (LND), an inhibitor of HK. LND significantly inhibited growth of 4 CCA cell lines tested in dose and time dependent fashion. Comparison the cytotoxic effects of LND and siRNA-HKII suggests the off target of LND above 100 μM. In addition, LND in non-cytotoxic doses could suppress migration and invasion of CCA cells. These results indicate the association of HKII in cholangiocarcinogenesis and progression and suggest the possibility of HKII as a therapeutic target for CCA. |
| Databáze: | OpenAIRE |
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