Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell

Abstract

Objective To investigate the anti carcinoma role of integrin targeted photodynamic therapy (PDT) on pancreatic carcinoma cells in vitro.Methods Pancreatic carcinoma cells SW1990 were divided into four groups:cells without quantum dots (QDs) and light-treated as blank control group,pure light-treated group,photosensitizer group and PDT group.The targeting of QDs-arginine,glycine,aspartic acid (RGD) and integrin probe was confirmed by laser confocal microscopy.And as a photosensitizer for photodynamic therapy,after treated for 48 hours the morphology changes of pancreatic carcinoma cells of each group were observed.After 48 hours,the cell proliferation,apoptosis and cell cycle changes were detected by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry (FCM).The expressions of myeloid cell leukemia-1 (Mcl-1),protein kinase B(Akt) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) were detected by reverse transcriptase polymerase chain reaction(RT-PCR).The amount of reactive oxygen species (ROS) of each group were evaluated by fluorescence probe.One-way ANOVA was performed for comparison between groups to analyze the treatment effects of PDT group.Results The QDs RGD probe could effectively targeting pancreatic carcinoma cells.The MTT results indicated that the relative inhibition rate of pancreatic carcinoma cells proliferation of PDT group was statistically higher than that of the other groups at 24,48,72 h (F=73.00,85.10,126.58; all P＜0.01).The FCM results revealed that the cell apoptosis rate of PDT group (17.860％ ±1.230％) was higher than that of the other groups (F=130.617,P＜0.01) and cell cycle G0/G1 phase (69.14％±2.63％) and S phase (24.41％ ± 2.67 ％) retardance was also significant (all P＜0.05).The expression of proliferation and apoptosis related gene Mcl-1 and Akt at mRNA level was lower than that of the other groups however the expression of apoptosis-inducing ligand TRAIL at mRNA level was higher than that of the other groups (F=567.456,446.817,145.238; all P＜0.05).The ROS level of PDT group was higher than that of the other groups (F=3262.559,P＜0.01).Conclusion PDT with a QDs-RGD probe could significantly inhibit pancreatic carcinoma cell proliferation and promote cell apoptosis. Key words: Pancreatic neoplasms; Integrins; Molecular probes; Photochemotherapy; Apoptosis