Suppression of tumor growth and pulmonary metastasis in murine osteosarcoma using gene therapy.
We evaluated the effect of gene therapy in the murine osteosarcoma cell line, LM8, which preferentially metastasizes to the lungs. LM8 cells were transduced with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase (lacZ). We investigated the cytotoxicity of LM8 cells bearing an HSV-tk gene after treatment with ganciclovir (GCV). LM8 cells bearing an HSV-tk gene were more sensitive than non-transduced cells. The remarkable inhibition of tumor growth and pulmonary metastases was confirmed in vivo. Our findings indicated that GCV kills tumor cells transduced with HSV-tk in vitro and in vivo.
Seto
Masashi
M
Department of Orthopaedic Surgery, Mie University School of Medicine, Tsu city, Mie prefecture 514, Japan. m-seto@clin.medic.mie-u.ac.jp
Yamazaki
Takashi
T
Sonoda
Jun
J
Matsumine
Akihiko
A
Shinto
Yoshitaka
Y
Uchida
Atsumasa
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir