Molecular therapy with recombinant antisense c-myc adenovirus for human gastric carcinoma cells in vitro and in vivo

Background and Aims: This study used a recombinant antisense c-myc adenovir us (Ad-ASc-myc) to evaluate how alterations of c-myc expression in the SGC7 901 human gastric carcinoma cells could influence the proliferation, apopto sis and the growth of human gastric tumors in nude mice. Methods: The human gastric carcinoma cell line, SGC7901, treated with Ad-AS c-myc or adenovirus recombinants carrying LacZ gene (Ad-LacZ) were analyzed by using X-gal stain, MTT, DNA ladder, TUNEL assay, flaw cytometric analys is, polymerase chain reaction and western blot in vitro. The tumorigenicity and experimental therapy in nude mice models were assessed in vivo. Results: The Ad-ASc-myc could strongly inhibit cell growth and induce apopt osis in SGC7901 cells. The proliferation of the Ad-ASc-myc-infected SGC7901 cells was reduced by 44.1%. The mechanism of killing gastric carcinoma cel ls by Ad-ASc-myc was found to be apoptosis, which was detected by the use o f a DNA ladder, TUNEL and flow cytometric analysis. Infection of Ad-ASc-myc in nude mice showed that all three mice failed to form tumors from the 7 t o 30 day period, compared with injection of Ad-LacZ and parent SGC7901 cell s. Experimental therapy on the nude mice bearing subcutaneous tumors of SGC 7901 cells showed that intratumor instillation of Ad-ASc-myc inhibited the growth of the turners. Recombinant antisense c-myc adenovirus-treated tumor s were inhibited by 68.9%, compared with tumors injected with Ad-LacZ and c ontrol (LacZ and phosphate-buffered saline). Conclusion: The expression of Ad-ASc-myc can inhibit growth and induce apop tosis of gastric cancer cells in vitro and in vivo and thus is a potential clinical utility in gene therapy for the treatment of gastric carcinoma. (C ) 2001 Blackwell Science Asia Pty Ltd.