Prevention of orthotopic human lung cancer growth by intratracheal instillation of a retroviral antisense K-ras construct.
An orthotopic human lung cancer model in nu/nu mice was used to study the effect of an antisense K-ras (AS-K-ras) retroviral construct on tumor growth in vivo. A 2-kilobase genomic AS-K-ras DNA fragment linked to a beta-actin promoter was cloned into the LNSX retroviral vector. The recombinant construct was packaged into GP+envAm12 cells and titers greater than 10(6) colony-forming units/ml were obtained. Irradiated (350 cGy) nu/nu mice were first inoculated intratracheally with 10(5) H460a human large cell lung carcinoma cells which have a codon 61 mutation of the K-ras oncogene. Three days later they received intratracheal instillation of viral supernatant (5 x 10(6) colony-forming units/ml) from either LNSX, LNSX-AS-K-ras, LNSX-sense-K-ras producer cells, or medium daily for 3 days. At autopsy, 30 days after tumor cell inoculation, 90% of the control mice had tumors whereas 87% of mice treated with the LNSX-AS-K-ras viral supernatant were free of tumors. The efficacy of the viral supernatant was dose dependent. Intratracheal administration of retroviral LNSX-AS-K-ras supernatant prevents the growth of human lung cancer cells implanted orthotopically in nu/nu mice.
Georges
R N
RN
Department of Thoracic Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Mukhopadhyay
T
T
Zhang
Y
Y
Yen
N
N
Roth
J A
JA
D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D002455:Cell Division; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics*; D014183:Transplantation, Heterologous
D016375:Antisense Elements (Genetics)