siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization.
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.
Immunology and Reproductive Biology Lab, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, P.R. China.
Qingling
Q
Wang
Yahong
Y
Huang
Yanhong
Y
Ni
Hui
H
Wang
Yayi
Y
Hou
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D019254:Genes, bcl-2; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D000078792:Midkine; D008928:Mitochondria / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000078792:Midkine; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases