RESUMO
AIM: To study distribution and accumulation of liposomal form of doxorubicin in human breast cancer cells of MCF-7 line and Dox-resistant subline MCF-7/Dox. METHODS: High performance liquid chromatography and laser confocal microscopy were used. RESULTS: It has been shown that conventional form of doxorubicin was more efficiently delivered to the MCF-7 cells already after 30 min of incubation amounting to its maximum concentration after 4 h. MCF-7/Dox cells are characterized by lower doxorubicin accumulation rate compared with parental cells. The quantity of accumulated liposomal form of doxorubicin is high in MCF-7 cells, and, what is important, Dox-resistant cells accumulated higher levels of liposomal form of doxorubicin than its conventional form. CONCLUSION: It has been shown that intracellular distribution and accumulation of liposomal forms of doxorubicin in parental and Dox-resistant MCF-7 cells differs from that of conventional doxorubicin.
Assuntos
Neoplasias da Mama/metabolismo , Doxorrubicina/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lipossomos , Microscopia ConfocalRESUMO
AIM: To compare the molecular profile and cell cycle of sensitive and resistant to doxorubicin MCF-7 breast cancer cells upon exposition to conventional or liposome-encapsulated forms of doxorubicin. METHODS: capital EM, Cyrilliccapital TE, Cyrilliccapital TE, Cyrillic-test, immunocytochemistry, flow cytometry. RESULTS: In sensitive MCF-7 cells the exposure to conventional but not liposomal form of doxorubicin decreased metallothionein (MT) expression demonstrating activation of MT-detoxification system. In doxorubicin-resistant cells (MCF-7/Dsmall o, Cyrillicsmall ha, Cyrillic) MT expression drastically decreased. Conventional but not liposomal form of doxorubicin reduced the levels of expression of steroid hormones receptors on MCF-7 sensitive cells. The exposure of MCF-7 cells to conventional form of doxorubicin resulted in the decrease of p53 expression and the increase of Bcl-2 expression. In MCF-7/Dsmall o, Cyrillicsmall ha, Cyrillic cells neither conventional nor liposomal form of doxorubicin altered Bcl-2 expression. The exposure of MCF-7 but not MCF-7/Dsmall o, Cyrillicsmall ha, Cyrillic to doxorubicin in conventional form caused cell cycle arrest in G0/G1. Upon exposure to doxorubicin in liposomal form, cell cycle blockage in G0/G1 phase was observed in both sensitive and resistant sublines. CONCLUSION: The differential effects of the conventional and liposomal forms of doxorubicin in sensitive and resistant cells have been demonstrated. Exposure of MCF-7 and MCF-7/Dsmall o, Cyrillicsmall ha, Cyrillic cells to doxorubicin in liposomal form alters the molecular profile and cell distribution over cell cycle phases.