The therapeutic effects of recombinant adenovirus RA538 on human gastric carcinoma cells in vitro and in vivo

摘要

AIM To evaluate the potential of RA-538 genetherapy for gastric carcinoma.METHODS Human gastric carcinoma cell lineSGC7901 treated with Ad-RA538 or Ad-LacZ wereanalysed by X-gal stain,MTT,DNA ladder,Tunel,flow cytometric analysis,PCR,andWestern Blot in vitro.The tumorigenicity andexperimental therapy in nude mice model wereassessed in vivo.RESULTS Ad-LacZ could efficiently transferthe LacZ gene into SGC7901 cells.X-gal-positivecells at MOI 25,50,100,and 200 were 90%,100%,100%,and 100% respectively.Ad-RA538could strongly inhibit cell growth and inducedapoptosis in SGC7901 cells.The proliferation ofthe Ad-RA538-infected SGC7901 cells wasreduced by 76.3%.The mechanism of killing ofgastric carcinoma cells by Ad-RA538 was foundto be apoptosis by DNA ladder,Tunel and flowcytometric analysis.The tumorigenicity in nudemice using Ad-RA538 showed that all three micefailed to form tumor from 7 to 30 days comparedwith Ad-LacZ and parent SGC7901 cells.Experimental therapy on the nude mice modelbearing subcutaneous tumor of SGC790| cells showed that intratumor instillation of Ad-RA538inhibited the growth of the tumors.Ad-RA538-treated tumors were inhibited by 60.66 %,compared with that of the tumor injected withAd-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.