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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.

Author information

1
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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

PMID:
18772588
DOI:
10.1159/000153655
[Indexed for MEDLINE]

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