In vitro and in vivo effect of IFNalpha on B16F10 melanoma in two models: subcutaneous (C57BL6J mice) and lung metastasis (Swiss mice).
Interferon alpha tends to be the only agent used to treat melanoma. The objective of this study was to assess the effect of interferon alpha on the growth of the B16F10 melanoma, both in vitro and in vivo. We study the in vitro effect of interferon alpha (250,000, 500,000 and 1,000,000 IU/ml) on the B16F10 melanoma cell line (at 24, 48 and 72 h) and the in vivo effect in a subcutaneous (1x10(6) cells; 300,000 IU) and a pulmonary metastatic model (5x10(5) cells/lateral vein of the tail; 300,000, 600,000 and 1,200,000 IU). Necropsy included a morphological and immunohistochemical study (subcutaneous model), while the number of superficial lung metastases, implantation percentage and growth and invasion indices were calculated in the latter model. In vitro, interferon alpha decreased cell survival in a time- and dose-dependent manner; 250,000 IU/ml: 77% (24h), 80% (48 h) and 92% (72 h); 500,000 IU/ml: 62% (24h), 32% (48 h), 20% (72 h); 1,000,000 IU/ml: 41% (24h), 16% (48 h), 10% (72 h). In the subcutaneous model, it reduced tumor weights (77.74%) and cell proliferation (70.8%), and increased necrotic areas (8%) and inflammatory infiltrates (34.46%). Metastatic model: 300,000 IU reduced pleural nodules by 38.79%, implantation by 59.42%, growth by 43.48%, invasion by 25.06%; the corresponding figures for 600,000 and 1,200,000 IU were 38.79, 59.42, 43.48, 25.06%, and 65.55, 84.98, 56.52, 66.19%, respectively. Interferon alpha inhibited cell proliferation in all the models and had immunomodulatory (subcutaneous model) and antimetastatic (pulmonary metastatic model) effects in vivo.
Martínez Conesa
Cristina
C
Department of Human Resources and Rural Development, Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), Murcia, Spain.
Alvarez Sánchez
Nuria
N
Vicente Ortega
Vicente
V
García Reverte
Juana
J
Pascual Carpe
Fernando
F
Campos Aranda
Matilde
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000637:transplantation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins