ABSTRACT
Objective To investigate the photochemotherapeutic effect and the main affecting factors of PSD-007 on human cervical cancer Hela in vitro.Methods Hela cells were treated with different concentrations of PSD-007 (0,3.125,6.25,12.5,25,50,100 μg/ml) for 2 h under the influence of low-level laser (635 nm) therapy at different doses (0,0.6,1.2,2.4,4.8,9.6 J/cm2).Then the OD values and survival rates of Hela cells were measured by MTT assay compared with breast cancer cells MCF-7 in same treatment.Hela cells were treated with 12.5 μg/ml of PSD-007 for 2 h and were treated with different intensities of laser (1.2,2.4,4.8 J/cm2).The cellular apoptosis rate and cell cycle phase distribution of Hela were measured by a flow cytometry (FCM).Results Survival rates of Hela cells declined with more than 25 μg/ml of PSD-007 only,and significant difference in the inhibitory between the PDT group and control group was observed (P＜0.05).The survival rates of Hela after PDT was decreased by the concentration of sensitizer and dose of laser.There were no significant differences of cell survival rates among the groups with concentrations more than 12.5 μg/ml and laser energy density more than 4.8 J/cm2.The FCM assay showed a G0/G1 cell cycle arrest in a time-dependent manner.Conclusions PSD-007 has a photodynamic effect on Hela in vitro.Photodynamic effect of PSD-007 was more significant in Hela than MCF-7.Less photosensitizer and laser energy density were needed.
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Objective To investigate the pharmacokinetic characteristics of PSD-007 in BN rats.Methods Blood of the BN rats was collected from the inner canthus after iv administration of PSD-007,and the plasma drug concentrations at different times were determined by fluorescent spectrometry.The best compartment model and the pharmacolinetic were calculated by the software of DNS 2.0.Results The elimination process of PSD-007 fitted three-compartment open model after iv administration.The principal pharmacokinetic parameters were t1/2α=0.096 h,t1/2β=1.299 h,t12γ=19.387 h,V1=0.259 L/kg,A UC=15.263 mg/(L ·h).Conclusions The sensitivity of fluorescent spectrometry was high and the operation is sinple and the progress is short.PSD-007 has fast absorption,quick effect and elimination without accumulation phenomenon.
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Objective To evaluate the combined effects of photodynamic therapy (PDT) with PSD-007 and cytarabine (Ara-c) on human acute promyelocyte leukemia cell HL-60.Methods The experiments were divided into four groups:control group,PDT-only groups (PDT 1-4 groups:the combination of PSD-007 concentrations (5 μg/ml and 7.5 μg/ml) and the energy density of laser (EDL) (1.2 J/cm2 and 2.4 J/cm2),Ara-c-only groups (Ara-c A group:0.3μg/ml,Ara-c B group:1.2μg/ml) and combination groups (the pair-wise combinations of the PDT doses and Ara-c doses above).All combination groups were treated with three treating methods,including P24A (the cells were treated with PDT for 24 h,and then cocultured with Ara-c for another 24 h),A24P (treated with Ara-c for 24 h before PDT,and then cocultured with PDT for 24 h),and PA24 (treated with the Ara-c and PDT for 24 h).CCK-8 method was used to test the cell viability,and the combined effect was analyzed using King formula.The changes of cell cycles were analyzed using flow cytometry.Results In the case of low-dose PDT,the combination groups showed coordinated effect with all three methods,whereas in the case of high-dose PDT,they showed additive or coordinated effect in P24A and A24P,but it showed antagonistic effect in the schedule of PA24.Cell cycles were inhibited to G0/G1 phase by both PDT and Ara-c.Conclusions Coordinated effects could be found when HL-60 cells were treated with the combination of Ara-c and PDT.The effects depended on the dose of Ara-c and PDT and the operation schedules.The effects at low dose were more obvious than that of high dose,and allowing a 24 h period in between the addition of PDT and Ara-c also promoted the effects.