Folate receptor-targeted cytarabine for inhibiting the proliferation of medulloblastoma and promoting its apoptosis: an in vitro experimental study

Abstract

Objective To investigate the folate receptor-targeted cytarabine (FR-Ara-C) for the proliferation inhibition and apoptosis promotion effect of the Daoy medulloblastoma cell lines. Methods The immunofluorescence and confocal laser scanning techniques were used to detect the expression of folate receptors-α (FRs-α) in Daoy cell lines. Methyl thiazolyl tetrazolium (MTT) colorimetric method was used to detect the proliferation inhibition rate after different concentrations (0.5-100.0×10-3 mmol/L FR-Ara-C and ordinary cytarabine [Ara-C]) acting on Daoy cells at different times (2-24 h) and their differences were compared. The group with the most obvious difference was selected for conducting AnnexinV-FITC/PI apoptosis detection. Results FRs-α expressed in both Daoy cell membrane and nucleus. When the same concentration of FR-Ara-C and Ara-C acted on Daoy cells at different times, the proliferation inhibition rate of FR-Ara-C was higher than that of Ara-C. There was significant difference (P<0.05); when the different concentrations of FR-Ara-C and Ara-C acted on Daoy cells at the same time, the proliferation inhibition rate of FR-Ara-C was higher than that of Ara-C. There was significant difference (P<0.05); when FR-Ara-C acted on for 8 h, the increased inhibition rate was most obvious compared with the Ara-C effect, 50% concentration of inhibition (IC50) at this time point was the optimal action concentration. Flow cytometry analysis showed that when 50×10-3 mmol/L concentration of FR-Ara-C and Ara-C acted on for 8 h, the apoptosis rates were 92.8±2.3% and 62.3±1.5%; when 10.0×10-3 mmol/L concentration of FR-Ara-C and Ara-C acted on for 8 h, the apoptosis rates were 87.1±2.4% and 44.7±1.7%; when the concentration was the same, the apoptosis rate was significantly higher than that of Ara-C after the action of FR-Ara-C. There was significant difference (P<0.05). Conclution FR-Ara-C has more significant proliferation inhibition and apoptosis promotion effect on medulloblastoma in vitro. Key words: Medulloblastoma; Folate receptor 1; Cytarabine; Inhibitory concentration 50