Lipofection of early passages of cell cultures derived from murine adenocarcinomas: in vitro and ex vivo testing of the thymidine kinase/ganciclovir system.
Early passages of cultured cells derived from four spontaneous Balb/c murine adenocarcinomas were used to explore the feasibility of a nonviral HSVtk-based suicide gene therapy system. After lipofection with pCMVtk, the transiently HSVtk expressing P07 (lung), M3, M05, and M38 (mammary gland) cells were, respectively, about 130-, 30-, 120-, and 170-fold more sensitive to ganciclovir (GCV) in vitro than their respective controls. Eighty percent of Balb/c mice subcutaneously inoculated with ex vivo pCMVtk-lipofected P07 cells, followed by intraperitoneal GCV injection for 7 days, displayed a complete inhibition of tumor growth for over 70 days. Control animals started to display tumors 13 days after inoculation. We present evidence showing that early passages of cultured tumor cells can efficiently express lipofected genes and that they are sensitive to the lipoplex-mediated HSVtk/GCV system.
Karara
Armando L
AL
Unidad de Transferencia Genética, Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires, Argentina.
Bumaschny
Viviana F
VF
Fiszman
Gabriel L
GL
Casais
Cecilia C
CC
Glikin
Gerardo C
GC
Finocchiaro
Liliana Me
LM
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D024201:Bystander Effect; D015774:Ganciclovir / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000201:enzymology*; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D000998:Antiviral Agents; D008081:Liposomes; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir