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*Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China;
Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China;
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China; and
Institute of Marine Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, Republic of China
Gene transfer of IL-27 to tumor cells has been proven to inhibit tumor growth in vivo by antiproliferation, antiangiogenesis, and stimulation of immunoprotection. To investigate the nonimmune mechanism of IL-27 that suppresses lung cancer growth, we have established a single-chain IL-27-transduced murine Lewis lung carcinoma (LLC-1) cell line (LLC-1/scIL-27) to evaluate its tumorigenic potential in vivo. Mice inoculated with LLC/scIL-27 displayed retardation of tumor growth. Production of IL-12, IFN-
, and cytotoxic T cell activity against LLC-1 was manifest in LLC/scIL-27-injected mice. Of note, LLC-1/scIL-27 exhibited decreased expression of cyclooxygenase-2 (COX-2) and PGE2. On the cellular level, the LLC/scIL-27 transfectants had reduced malignancy, including down-regulation of vimentin expression and reduction of cellular migration and invasion. The suppression of tumorigenesis by IL-27 on lung cancer cells was further confirmed by the treatment with rIL-27 on the murine LLC-1 and human non-small cell lung carcinoma (NSCLC) cell lines. PGE2-induced vimentin expression, movement, and invasiveness were also suppressed by the treatment with rIL-27. Our data show that IL-27 not only suppresses expression of COX-2 and PGE2 but also decreases the levels of vimentin and the abilities of cellular migration and invasion. Furthermore, inoculation of LLC/scIL-27 into immunodeficient NOD/SCID mice also exhibited reduced tumor growth. Our data indicate that IL-27-induced nonimmune responses can contribute to significant antitumor effects. Taken together, the results suggest that IL-27 may serve as an effective agent for lung cancer therapy in the future.
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1 The work was supported by grants from the National Science Council (NSC 95-2320-B-010-022-MY3 and NSC97-2811-B010-014), the Veterans General Hospital University System of Taiwan (VGHUST) Joint Research Program, Tsou’s Foundation (VGHUST 97-P6-31), Taipei City Hospital, and the Ministry of Education (Aim for the Top University Plan), Republic of China.
2 Address correspondence and reprint requests to Dr Kuang-Hui Sun, Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, 155 Section 2, Lie-Nong Street, Taipei, Taiwan 112, Republic of China. E-mail address: khsun{at}ym.edu.tw or Dr. Shye-Jye Tang, Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan 202, Republic of China. E-mail address: tsj{at}mail.ntou.edu.tw
3 Abbreviations used in this paper: COX, cyclooxygenase; EMT, epithelial-mesenchymal transition; LLC-1, Lewis lung carcinoma-1; NOD, nonobese diabetic; NSCLC, non-small cell lung cancer; RT-qPCR, RT-quantitative PCR; scIL-27, single-chain IL-27; VEGF, vascular endothelial growth factor.
4 The online version of this article contains supplemental material.
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