Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice.
OBJECTIVE
To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice.


METHODS
Forty-five 5-week-old female BALB/c nude mice.


METHODS
1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined.


RESULTS
Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group.


CONCLUSIONS
9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs.
Hong
S H
SH
Pediatrics Oncology Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
Kadosawa
T
T
Mochizuki
M
M
Matsunaga
S
S
Nishimura
R
R
Sasaki
N
N
D000077556:Alitretinoin; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000077556:Alitretinoin; D014212:Tretinoin