Comparison of the in vitro and in vivo effects of retinoids either alone or in combination with cisplatin and 5-fluorouracil on tumor development and metastasis of melanoma.
OBJECTIVE
Retinoids have previously been reported to inhibit proliferation of melanoma cell lines in vitro. However, the relative antimetastatic efficacy of various retinoids on melanoma in vivo is unknown. Therefore, we investigated the effects of different retinoids on the invasion and metastasis of murine melanoma B16-F10 cells in vitro and in vivo. Based on the findings, the antitumor effects of a selected retinoid either alone or in combination with cisplatin were also investigated in a preclinical mouse melanoma model.


METHODS
Cell proliferation and invasion analyses of murine melanoma B16-F10 cells were assessed in the presence of different retinoids, either alone or in combination with cisplatin (CDDP) or 5-fluorouracil (5-FU). Experimental lung metastasis assay was performed in this study to investigate the antimetastatic efficacy of retinoids. Additionally, a mouse melanoma model was used to assess the antitumor efficacy of a selected retinoid in combination with cisplatin.


RESULTS
Retinoids showed significant antiproliferation and anti-invasion effects on murine melanoma B16-F10 cells. Pretreatment with retinoids increased the sensitivity to CDDP but not to 5-FU in in-vitro. Moreover, the number of metastatic colonies formed in the lungs of mice injected intravenously with B16-F10 cells was significantly reduced by injecting the respective retinoid once a day for 10 days. Treatment with a combination of cisplatin and 13-cis-retinoic acid resulted in a significant reduction in primary tumor size and the number of lung metastatic nodules in melanoma-bearing mice.


CONCLUSIONS
These results suggest that retinoids not only exhibit antimetastatic effect, but also enhance the antitumor activity of cisplatin in vivo.
Liu
Xin
X
Department of Pharmacy, National University of Singapore, Singapore.
Chan
Sui Yung
SY
Ho
Paul Chi-Lui
PC
D017255:Acitretin / Q000494:pharmacology / Q000627:therapeutic use; D000077556:Alitretinoin; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005050:Etretinate / Q000494:pharmacology / Q000627:therapeutic use; D005347:Fibroblasts / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D015474:Isotretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D012176:Retinoids; D000077556:Alitretinoin; D014212:Tretinoin; D005050:Etretinate; D015474:Isotretinoin; D017255:Acitretin; D002945:Cisplatin; D005472:Fluorouracil