Recombinant Human Interleukin-24 Suppresses Gastric Carcinoma Cell Growth In Vitro and In Vivo

Su YanCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Haifeng ZhangCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Yufeng XieCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Weihua ShengCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Jim XiangCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Zhenmin YeCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Weichang ChenCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Canada

Jicheng YangCell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China, Digestive Department, the First Affiliated Hospital of Soochow University, Suzhou, China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, CanadaCorrespondence[email protected]

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ABSTRACT

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-β-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-α, and IFN-γ. 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.

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Recombinant Human Interleukin-24 Suppresses Gastric Carcinoma Cell Growth In Vitro and In Vivo

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