Abstract |
The abiraterone acetate (AA) is a drug used to castration-resistant
prostate cancer (CPRC) treatment. The introduction of AA in therapy
significantly increased the survival of patients with CPRC. However, AA
resistance development is common in most of the patients. Therefore, the
development of an AA-resistant cell line is useful for understanding the
molecular mechanisms involved in this process and to the development of
novel therapeutic agents. An AA-resistant cell line was established from
the LNCAP cell line after incubated with increasing AA concentration until
reaches the IC50 for the cell line. After that, the resistant confirmation
and characterization of the cell line were proceeded. The fold-resistance
and cell proliferation rate were performed by MTT assay. Cell cycle
distribution and express of cancer stem cells markers (CD133 and CD44)
were evaluated by FACS analysis. In comparison to parental cell line, the
AA-resistant cell line has a slower growth rate and a 1,4-fold increase in
resistance to AA. No differences were observed regarding to cell cycle
distribution, cell morphology, and expression of CD133 and CD44 markers
between the resistant and parental cell lines. Additional characterization
parameters such as specific miRNAs expression and ARV7 protein expression
are still required. Therefore, an AA resistance induction in a prostate
cancer cell line (LNCAP) was achieved as well as the cell line
characterization, at least in part, allowing further studies of new
resistance mechanisms and new treatment strategies.
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