Recombinant human interleukin-24 suppresses gastric carcinoma cell growth in vitro and in vivo.
Previous studies have demonstrated that interleukin-24 [IL-24; originally called melanoma differentiation associated gene-7 (mda-7)] as a novel tumor suppressor gene has tumor-suppressive activity against a broad spectrum of human cancers. However, the therapeutic effect of the recombinant human IL-24 (rhIL-24) protein purified from prokaryotic cells on gastric cancer has not been reported. In this study, we purified soluble rhIL-24 using Q-Sepharose column after the denaturing and renaturing process from the protein of Escherichia coli BL21 transfected with pET-21a(+)-hIL-24 vector and treated by isopropyl-beta-D-1-thiogalactopyranoside (IPTG) for enhanced expression of transgene rhIL-24. We demonstrated that rhIL-24 was capable of inducing in vitro apoptosis of SGC7901 gastric cancer cells and activating peripheral blood mononuclear cellsto secrete cytokines such as IL-6, TNF-alpha, and IFN-gamma. We also showed that rhIL-24 was able to inhibit formation of blood capillaries on chicken embryonic allantois and in vivo tumor angiogenesis leading to suppressing SGC7901 gastric cancer cell growth in vitro and in vivo possibly due to its downregulation of Bcl-2/Bax ratio, VEGF (vascular endothelial growth factor), and CD34. Therefore, our results indicate that rhIL-24 has potent suppressive effect on human SGC7901 gastric carcinoma cell line and warrant its further investigation for therapeutic application against gastric cancer.
Yan
Su
S
Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China.
Zhang
Haifeng
H
Xie
Yufeng
Y
Sheng
Weihua
W
Xiang
Jim
J
Ye
Zhenmin
Z
Chen
Weichang
W
Yang
Jicheng
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099180:Interleukin-24
D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D016207:Cytokines; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D000099180:Interleukin-24; C494826:BAX protein, human; C467484:VEGFA protein, human