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KMID : 0620920180500080101
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Experimental & Molecular Medicine
2018 Volume.50 No. 8 p.101 ~ p.101
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Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells
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He Lingfeng
Zhu Hong
Zhou Shiying
Wu Ting
Wu Huan
Yang Huan
Mao Huiwen
SekharKathera Chandra
Janardhan Avilala
Edick Ashlin M.
Zhang Anna
Hu Zhigang
Pan Feiyan
Guo Zhigang
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Abstract
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Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. 5-Fluorouracil (5-FU) is widely used in the treatment of cancers, but its antineoplastic activity is limited in drug-resistant cancer cells. To investigate the detailed mechanism of 5-FU resistance, we developed a model of 5-FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell line. We found that the drug-resistant cells demonstrated high expression of TCF4 and β-catenin, indicating an upregulated Wnt pathway. A microarray analysis revealed that the suppression of the checkpoint kinase 1 (CHK1) pathway explained the resistance to 5-FU, especially in p53 wild-type cancer cells such as HCT-8. Our data also demonstrated that the CHK1 pathway is suppressed by the Wnt pathway in 5-FU-resistant cells. In summary, we have discovered a novel mechanism for 5-FU resistance mediated by histone deacetylation, which also revealed the crosstalk between the Wnt pathway and CHK1 pathway.
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KEYWORD
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Apoptosis, Cancer therapeutic resistance
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