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Experimental study on targeting and inhibiting hexokinase 2 by miR-143 for treatment of breast cancer

MIAO Ying1, ZHANG Ling-fei2, LIANG Sheng3, SHI Shuo1, LIU Mo-fang2, LI Biao1   

  1. 1.Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2.Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 3.Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2014-08-28 Published:2014-09-02
  • Supported by:

    National Natural Science Foundation of China, 81271610

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Abstract:

Objective To verify the therapeutic effect of miR-143 on breast cancer cell line MDA-MB-231 by targeting and inhibiting hexokinase 2 (HK2) and changing its energy metabolism and to explore the value of 18F-FDG and 18F-FLT for evaluating the therapeutic effectiveness. Methods Breast cancer cells were divided into three groups, i.e. the test group (transfected by the miR-143 mimic), the negative control group (transfected by scramble sequence of small RNA), and the blank group (no treatment). Variations of expressions of mRNA and protein level of HK2 before and after the treatment were detected by qRT-PCR and Western blot. The variations of rates of glucose metabolism and lactic acid production were detected. The variations of proliferative ability of tumor cells were detected by the MTT. The dynamic variations of 18F-FDG and 18F-FLT uptake were measured to determine the value of two tracers for evaluating the therapeutic effectiveness. Results The expressions of mRNA and protein level of HK2 of the test group decreased. Compared to the negative control group, the rates of glucose metabolism and lactic acid production and the proliferative ability significantly decreased in the test group. After cells were cultured by 18F-FDG and 18F-FLT for 30, 60, 90, and 120 min, the uptake of 18F-FDG and 18F-FLT showed time-dependent increase and the uptake of 18F-FDG was lower than that of 18F-FLT at each time point. At 30 min, the uptake of 18F-FDG of the test group was significantly lower than that of the negative control group (21.81±2.75 vs 36.71±4.36). The difference was statistically significant (P<0.05). The uptake of 18F-FLT of two groups showed no significant difference (12.03±1.53 vs 15.23±2.31, P>0.05). At 60 min, the differences of the uptake of 18F-FDG and 18F-FLT of two groups were statistically significant (P<0.05). Conclusion The therapeutic effect of miR-143 is achieved by targeting and inhibiting HK2 and changing its energy metabolism. 18F-FDG is better for evaluating the therapeutic effectiveness.

Key words: targeted therapy, breast cancer, microRNA, 18F-FDG, 18F-FLT