Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 2000; 6(6): 855-860
Published online Dec 15, 2000. doi: 10.3748/wjg.v6.i6.855
The therapeutic effects of recombinant adenovirus RA538 on human gastric carcinoma cells in vitro and in vivo
Jie Ping Chen, Chen Lin, Cai Pu Xu, Xue Yan Zhang, Ming Wu
Jie Ping Chen, Cai Pu Xu, Department of Gastroenterology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China
Chen Lin, Xue Yan Zhang, Ming Wu, National Laboratory of Molecular Oncology, Department of Cell Biology, Cancer Institute, Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China
Jie Ping Chen, graduated from Third Military Medical University as a Ph.D. postgraduate in 1998, postdoctoral fellow in Second Affiliated Hospital of Chongqing University of Medical Sciences, associate professor of gastroenterology, major in Helicobacter pylori infection and gastric cancer, having 30 papers published.
Author contributions: All authors contributed equally to the work.
Supported by the National 863 Science and Technology Fund of China, No.Z20-01-02
Correspondence to: Dr. Jie Ping Chen, Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Email: jpchen@public.cta.cq.cn
Telephone: 0086-23-65318301 Ext.73094
Received: April 3, 2000
Revised: April 19, 2000
Accepted: April 26, 2000
Published online: December 15, 2000
Abstract

AIM: To evaluate the potential of RA-538 gene therapy for gastric carcinoma.

METHODS: Human gastric carcinoma cell line SGC7901 treated with Ad-RA538 or Ad-LacZ were analysed by X-gal stain, MTT, DNA ladder, Tunel, flow cytometric analysis, PCR, and Western Blot in vitro. The tumorigenicity and experimental therapy in nude mice model were assessed in vivo.

RESULTS: Ad-LacZ could efficiently transfer the LacZ gene into SGC7901 cells. X-gal-positive cells at MOI 25, 50, 100, and 200 were 90%, 100%, 100%, and 100% respectively. Ad RA538 could strongly inhibit cell growth and induced apoptosis in SGC7901 cells. The proliferation of the Ad-RA538-in fected SGC7901 cells was reduced by 76.3%. The mechanism of killing of gastric carcinoma cells by Ad-RA538 was found to be apoptosis by DNA ladder, Tunel and flow cytometric analysis. The tumorigenicity in nude mice using Ad-RA538 showed that all three mice failed to form tumor from 7 to 30 d compared with Ad-LacZ and parent SGC7901 cells. Experimental therapy on the nude mice model bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 inhibited the growth of the tumors. Ad-RA538-treated tumors were inhibited by 60.66%, compared with that of the tumor injected with Ad-LacZ and mock.

CONCLUSION: The expression of Ad-RA538 can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. Ad-RA538 can be used potentially in gene therapy for gastric carcinoma.

Keywords: stomach neoplasms/therapy; adenoviridae; apoptosis; gene therapy; polymerase chain reaction; genes MYC; flow cytometry