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


CONCLUSIONS
Our findings suggest that targeting HK II may be beneficial for patients with colon cancer treated with 5-FU.
Peng
Qiu-Ping
QP
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Zhou
Jin-Ming
JM
Zhou
Qi
Q
Pan
Feng
F
Zhong
Da-Ping
DP
Liang
Hou-Jie
HJ
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D034622:RNA Interference
D006593:Hexokinase; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D005472:Fluorouracil