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Chemotherapy. 2008;54(5):357-63. doi: 10.1159/000153655. Epub 2008 Sep 5.

Downregulation of the hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil.

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Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.



Extensive trials have indicated that cancer cells with high glycolytic activity exhibit decreased sensitivity to anticancer agents. Moreover, recent research has proven that specific inhibitors of hexokinase (HK) II, a key glycolytic enzyme, may enhance the activity of anticancer drugs. The aim of this study was to investigate the effect and mechanisms of HK II on chemosensitivity of a colon cancer cell line (LoVo) to 5-fluorouracil (5-FU).


HK II gene expression was downregulated by RNA interference in the colon cancer cell line LoVo, which was detected by Western blot analysis. Then the IC(50) value of 5-FU was determined in LoVo cells via MTT assay. In addition, cell apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry and caspase-3 activity by its substrate color reaction.


In LoVo cells, HK II downregulation resulted in a decreased IC(50) value of 5-FU and increased apoptosis. Furthermore, HK II downregulation resulted in a decreased MPP and activation of caspase-3.


Our findings suggest that targeting HK II may be beneficial for patients with colon cancer treated with 5-FU.

[Indexed for MEDLINE]

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