Gastric Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2005; 11(21): 3204-3211
Published online Jun 7, 2005. doi: 10.3748/wjg.v11.i21.3204
Anti-gastric cancer active immunity induced by FasL/B7-1 gene-modified tumor cells
Shi-Ying Zheng, De-Chun Li, Zhi-De Zhang, Jun Zhao, Jin-Feng Ge
Shi-Ying Zheng, Jun Zhao, Jin-Feng Ge, Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China
De-Chun Li, Zhi-De Zhang, Department of General Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Shi-Ying Zheng, Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China. syzheng88@ sina.com
Telephone: +86-512-65263570
Received: June 19, 2004
Revised: June 20, 2004
Accepted: August 6, 2004
Published online: June 7, 2005
Abstract

AIM: To study the activation of cytotoxic T lymphocytes (CTLs) against gastric cancer cells induced by FasL/B7-1 (FB-11) gene-modified tumor cells, and to explore whether co-expression of FasL and B7-1 in SGC-7901 tumor cells could initiate synergistic antitumor effect.

METHODS: FasL and B7-1 genes were transfected into human SGC-7901 gastric cancer cells with adenovirus vectors. The positive clones were selected by G418. FasL and B7-1 genes were detected by flow cytometry and RT-PCR. Abdominal infiltrating lymphocytes and sensitized spleen cells were obtained from mice that were immunized with SGC-7901/FB-11 or wild type SGC-7901 cells intraperitoneally, and cytotoxicity of these CTLs against tumor cells was determined by MTT assay.

RESULTS: Flow cytometry and RT-PCR showed that FasL and B7-1 genes were highly expressed. FasL and B7-1 transfected cancer cells had a high apoptosis index. DNA laddering suggested that FasL and B7-1 genes induced gastric cancer cell apoptosis. FasL+/B7-1+SGC-7901 cells (SGC-7901/FB-11) were inoculated subcutaneously in the dorsal skin of C57BL/6 mice and then decreased their tumorigenicity greatly (z = 2.15-46.10, P<0.01). SGC-7901/FB-11 cell-sensitized mice obtained protective immune activity against the rechallenge of wild type SGC-7901 cells (z = 2.06-44.30, P<0.05). The cytotoxicity of CTLs induced by SGC-7901/FB-11 cells against SGC-7901 was significantly higher than that of CTLs activated by wild-type SGC-7901 cells (84.1±2.4% vs 30.5±2.3%, P<0.05).

CONCLUSION: FasL and B7-1 genes can effectively promote the activity of CTLs against gastric cancer cells. FasL/B7-1 molecules play an important role in CTL cytotoxicity.

Keywords: Gastric cancer, FasL gene, B7-1 gene, Gene therapy, Synergistic effect