RESUMO
BACKGROUND: One possible mechanism of chemotherapeutic resistance in patients with metastatic prostate cancer is the overexpression of P-glycoprotein. Additional tumor models are necessary to study this phenomenon. MATERIALS AND METHODS: Doxorubicin resistant rat prostate cancer cell lines were developed by increasing doxorubicin levels in cell culture. RESULTS: The MDR lines (AT3B-1, AT3B-2, MLLB-1, and MLLB-2) were more resistant to vinblastine compared to controls. When P-glycoprotein was blocked, the AT3 MDR lines demonstrated efflux activity. Injection of AT3 MDR lines into rats followed by doxorubicin treatment produced larger tumors compared to the parental controls. CONCLUSIONS: MDR rat prostate cancer cells were developed. AT3B-1 and AT3B-2 cell lines have drug efflux pump ability, whereas the MLLB-1 and MLLB-2 may not, suggesting alternative key mechanisms other than P-glycoprotein overexpression. These new cell lines are being used to study chemotherapy resistance in prostate cancer.
Assuntos
Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Resistência a Múltiplos Medicamentos , Neoplasias da Próstata/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Masculino , Neoplasias da Próstata/tratamento farmacológico , Ratos , Células Tumorais Cultivadas , Vimblastina/farmacocinética , Vimblastina/toxicidadeRESUMO
The nuclear matrix has been linked to several important cellular functions within cells, such as DNA organization and replication, as well as regulation of gene expression. It has been reported that the nuclear matrix protein composition is altered in cells grown on different extracellular matrices in vitro. This study examined the nuclear matrix protein composition of tumors produced by MAT-LyLu (MLL) rat prostate tumor cells implanted at different organ sites within the rat. When high resolution two-dimensional gels were utilized to compare nuclear matrix protein composition to the prostate orthotopic tumor, it was found that there were distinct protein differences depending upon where the tumor grew. In particular, there were 14 proteins found in the lung, six proteins found in intramuscular, 17 proteins is the heart, and five proteins in the tail vein tumor tissue that were not present in the prostate orthotopic tumor tissue. Therefore, this study adds evidence to support that the nuclear matrix composition of a cell is dependent, at least in part, by the extracellular matrix and/or different cellular environments and may have a role in site-specific differences in tumor properties.
