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siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization

  • Published:
Journal of Biomedical Science

Abstract

Midkine (MK), a heparin-binding growth factor, is expressed highly in various malignant tumors, so it acts as attractive therapeutic target. In the present study, we used siRNA targeting MK to downregulate human MK expression in human gastric cancer cell line BGC823 and SGC7901 so as to determine the advantages of this anticancer therapeutic. The cell proliferation was evaluated by a WST-8 (4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate sodium salt) assay and colony formation assay. Apoptosis was determined by flow cytometer analysis and colorimetric assay. Our results showed that the BGC823 and SGC7901 cell growth were significantly inhibited by knockdown of MK gene. The loss of mitochondrial membrane potential, release of cytochrome c from the mitochondria into cytosol and increased activity of caspase-3, 8 and 9 occurred concomitantly with inhibition of MK gene. These results indicated that siRNA targeting MK gene can inhibit gastric cancer cells growth and induce apoptosis via mitochondrial depolarization and caspase-3 activation. MK siRNA may be a promising novel and potential therapeutic strategy for the treatment of gastric cancers.

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Acknowledgements

This work was supported by the Scientific Research Foundation of Graduate School of Nanjing University, the Foundation for Key Program of Ministry of Education, China (Grant No. 02111) and the 985-II Program of Nanjing University.

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Authors and Affiliations

  1. Immunology and Reproductive Biology Lab, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, P.R. China

    Qingling Wang, Yahong Huang, Yanhong Ni, Hui Wang & Yayi Hou

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  1. Qingling Wang
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  2. Yahong Huang
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  3. Yanhong Ni
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  4. Hui Wang
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  5. Yayi Hou
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Correspondence to Yayi Hou.

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Wang, Q., Huang, Y., Ni, Y. et al. siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization. J Biomed Sci 14, 783–795 (2007). https://doi.org/10.1007/s11373-007-9192-0

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  • DOI: https://doi.org/10.1007/s11373-007-9192-0

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