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World J Gastroenterol. Apr 21, 2006; 12(15): 2450-2454
Published online Apr 21, 2006. doi: 10.3748/wjg.v12.i15.2450
Antisense angiopoietin-1 inhibits tumorigenesis and angiogenesis of gastric cancer
Jun Wang, Kai-Chun Wu, De-Xin Zhang, Dai-Ming Fan
Jun Wang, Kai-Chun Wu, De-Xin Zhang, Dai-Ming Fan, State Key Laboratory of Cancer Biology & Institute of Digestive Disease, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Supported by the National Natural Science Foundation of China, No. 30130260,30225039
Correspondence to: Dr. Kai-Chun Wu, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China. kaicwu@fmmu.edu.cn
Telephone: +86-29-84775229 Fax: +86-29-82539041
Received: September 2, 2005
Revised: November 2, 2005
Accepted: November 18, 2005
Published online: April 21, 2006

AIM: To investigate the effect of angiopoietin-1 (Ang-1) on biological behaviors in vitro and tumorigenesis and angiogenesis in vitro of human gastric cancer cells.

METHODS: Human full-length Ang-1 gene was cloned from human placental tissues by RT-PCR method. Recombinant human Ang-1 antisense eukaryotic expression vector was constructed by directional cloning, and transfected by lipofectin method into human gastric cancer line SGC7901 with high Ang-1 expression level. Inhibition efficiency was confirmed by semi- quantitive PCR and Western blot method. Cell growth curve and cell cycle were observed with MTT assays and flow cytometry, respectively. Nude mice tumorigenicity test was employed to compare in vitro tumorigenesis of cells with Ang-1 suppression. Microvessel density (MVD) of implanted tumor tissues was analyzed by immunohistochemistry for factor VIII staining.

RESULTS: Full-length Ang-1 gene was successfully cloned and stable transfectants were established, namely 7Ang1- for antisense,and 7901P for empty vector transfected. 7Ang1- cells showed down-regulated Ang-1 expression, while its in vitro proliferation and cell cycle distribution were not significantly changed. In contrast, xenograft of 7Ang1- cells in nude mice had lower volume and weight than those of 7901P after 30 days’ implantation (P < 0.01, 293.00 ± 95.54 mg vs. 624.00 ± 77.78 mg) accompanied with less vessel formation with MVD 6.00±1.73 compared to 7901P group 8.44±1.33 (P < 0.01).

CONCLUSION: Ang-1 may play an important role in tumorigenesis and angiogenesis of gastric cancer, and targeting its expression may be beneficial for the therapy of gastric cancer.

Keywords: Angiogenesis, Angiopoietin, Stomach neoplasms, Gene therapy