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

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.

• Authors: Qiu-Ping Peng, Jin-Ming Zhou, Qi Zhou, Feng Pan, Da-Ping Zhong, Hou-Jie Liang
• Journal: Chemotherapy (Chemotherapy) Vol. 54 Issue 5 Pg. 357-63 ( 2008) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 18772588 (Publication Type: Journal Article)
• Copyright: 2008 S. Karger AG, Basel.

Chemical References

• Hexokinase
• Caspase 3
• Matrix Metalloproteinases
• Fluorouracil

Topics

• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, enzymology, pathology)
• Down-Regulation
• Enzyme Activation (drug effects)
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Hexokinase (genetics, metabolism)
• Humans
• Matrix Metalloproteinases (metabolism)
• RNA Interference