J Chen1, C Lin, C Xu, X Zhang, M Fu, M Wu. 1. Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 P. R. China. jpchen@public.cta. cq.cn
Abstract
OBJECTIVE: Compare the biological effects of recombinant RA538 and antisense c-myc adenovirus on human gastric cancer cell line (SGC7901) and explore the molecular mechanism in vitro and in vivo. METHODS: SGC7901 cells were treated with Ad-RA538, Ad-AS c-myc or Ad-LacZ. MTT, DNA ladder, TUNEL and FCM, RT-PCR, Western blot analysis, the tumorigenicity in nude mice and experimental therapy of the nude mice were used. RESULTS: Ad-RA538 and Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis of SGC7901 cells. The growth of the Ad-RA538- and Ad-ASc-myc-infected SGC7901 cells were inhibited by 76.3% and 44.1% respectively. The over expression of RA538 and ASc-myc could down-regulate expression of c-myc, bcl-2 and cyclinD1 gene and up-regulate expression of bax gene, but it could not regulate expression of p53, p16, TGase, and ras gene. The tumorigenicity of Ad-RA538 or Ad-ASc-myc in nude mice showed that three of three mice failed to form tumor, compared with Ad-LacZ and parent SGC7901 cells from 7 to 30 days. Experimental therapy of the nude mice bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 and Ad-ASc-myc inhibited the growth of the tumors. Ad-RA538- and Ad-ASc-myc-treated tumors were inhibited by 60.7% or 68.9% respectively, compared with the tumor injected with Ad-LacZ and mock. CONCLUSION: The expression of Ad-RA538 and Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. RA538 and ASc-myc relate to c-myc, bcl-2, cyclinD1 and bax gene closely and have noticeable biologic effects on gastric cancer cells.
OBJECTIVE: Compare the biological effects of recombinant RA538 and antisense c-myc adenovirus on humangastric cancer cell line (SGC7901) and explore the molecular mechanism in vitro and in vivo. METHODS: SGC7901 cells were treated with Ad-RA538, Ad-AS c-myc or Ad-LacZ. MTT, DNA ladder, TUNEL and FCM, RT-PCR, Western blot analysis, the tumorigenicity in nude mice and experimental therapy of the nude mice were used. RESULTS: Ad-RA538 and Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis of SGC7901 cells. The growth of the Ad-RA538- and Ad-ASc-myc-infected SGC7901 cells were inhibited by 76.3% and 44.1% respectively. The over expression of RA538 and ASc-myc could down-regulate expression of c-myc, bcl-2 and cyclinD1 gene and up-regulate expression of bax gene, but it could not regulate expression of p53, p16, TGase, and ras gene. The tumorigenicity of Ad-RA538 or Ad-ASc-myc in nude mice showed that three of three mice failed to form tumor, compared with Ad-LacZ and parent SGC7901 cells from 7 to 30 days. Experimental therapy of the nude mice bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 and Ad-ASc-myc inhibited the growth of the tumors. Ad-RA538- and Ad-ASc-myc-treated tumors were inhibited by 60.7% or 68.9% respectively, compared with the tumor injected with Ad-LacZ and mock. CONCLUSION: The expression of Ad-RA538 and Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. RA538 and ASc-myc relate to c-myc, bcl-2, cyclinD1 and bax gene closely and have noticeable biologic effects on gastric cancer cells.