Adenovirus-mediated suicide gene transfer to small cell lung carcinoma using a tumor-specific promoter.
The gastrin-releasing peptide (GRP) is expressed in most types of small cell lung carcinoma (SCLC) and the GRP promoter is thought to be potentially useful for tumor-specific expression of the suicide gene in SCLC. We constructed an adenovirus containing the herpes simplex thymidine kinase suicide gene driven by the GRP promoter (AdGRP-TK) and transfected it into GRP-expressing SCLC cells (SBC5) to confer sensitivity to ganciclovir (GCV). After infection with AdGRP-TK, SBC5 cells became more sensitive to GCV in vitro. In nude mice, a subcutaneously-inoculated tumor of SBC5 cells infected with AdGRP-TK in advance regressed completely after intraperitoneal administration of GCV. These results suggest that adenovirus-mediated gene transfer of the suicide gene followed by pro-drug treatment may be applicable to SCLC.
Morimoto
E
E
Pulmonary Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Inase
N
N
Mlyake
S
S
Yoshizawa
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D019886:Gastrin-Releasing Peptide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D011355:Prodrugs; D012333:RNA, Messenger; D019886:Gastrin-Releasing Peptide; D013937:Thymidine Kinase; D015774:Ganciclovir