RESUMO
Conjugates of carminomycin (Cm) with alpha-fetoprotein (AFP) and epidermal growth factor (EGF) were prepared and their cytotoxic activities were studied in vitro. Both conjugates showed cytotoxic activity which exceeded that of free Cm in tumor cell cultures of MCF-7, SKOV3, QOS, P388 and B16 cells. The antitumor effects of the conjugates were studied in vivo in mice with subcutaneous tumors of B16 and P388 cells. The Cm-AFP and Cm-EGF conjugates inhibited tumor growth and noticeably increased the mean life span in experimental animals. Our results suggest that the therapeutic activity of Cm can be significantly enhanced by conjugation to AFP or EGF.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Carrubicina/farmacologia , Fator de Crescimento Epidérmico/farmacologia , alfa-Fetoproteínas/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Carrubicina/administração & dosagem , Carrubicina/análogos & derivados , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/análogos & derivados , Humanos , Leucemia P388/tratamento farmacológico , Leucemia P388/patologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Transplante de Neoplasias , Células Tumorais Cultivadas/efeitos dos fármacos , alfa-Fetoproteínas/administração & dosagem , alfa-Fetoproteínas/químicaRESUMO
Epidermal growth factor (EGF) was used as a vector for targeted delivery of phthalocyanines to tumor cells. The conjugates of EGF with disulfochloride aluminum phthalocyanine [Pc(Al)] and disulfochloride cobalt phthalocyanine [Pc(Co)] were synthesized. The cytotoxic activity of the conjugates against the human breast carcinoma cell line MCF-7 was determined. The cytotoxic activity of the EGF-Pc(Co) conjugate was 4.5 times higher than that of the EGF-Pc(Al) conjugate. The antitumor activity of the EGF-Pc(Co) conjugate was also studied in vivo in murine melanoma B16. Compared to free Pc(Co), intravenous injections of Pc(Co) conjugated with EGF inhibited tumor development and increased mean life span and mean survival time of experimental animals.
