ABSTRACT
Background:Pancreatic cancer is obscure in onset and progresses rapidly with very poor prognosis. Photodynamic therapy( PDT)has been developed as a novel anti-tumor treatment modality since 1980s. At present,there are only limited researches on pancreatic cancer treated with PDT in vivo. Aims:To investigate the efficacy of quantum dots-RGD ( QDs-RGD)based PDT combined with gemcitabine for treatment of pancreatic cancer xenograft in nude mice. Methods:QDs-RGD probe was synthesized and nude mice bearing pancreatic cancer xenograft was established. Nude mice were imaged at 1,5,10 and 24 hours after injection of QDs-RGD and QDs by in vivo imaging system. Forty model nude mice were randomly divided into five groups:control group( without any treatment),simple illumination group( laser 630 nm, 120 J/cm2,20 min),PDT group(QDs-RGD 0. 5 nmol+laser irradiation),gemcitabine group(gemcitabine 50 mg/kg)and combination group(QDs-RGD 0. 5 nmol+laser irradiation+gemcitabine 50 mg/kg). All the nude mice were sacrificed 18 days later. Tumor weight and volume were measured and tumor inhibition rate was calculated. Results:Fluorescence of tumor was shown 1 hour after injection and became clearest at the 5th hour,then showing a decrescendo trend. Density of QDs surrounding tumor was significantly less than that of QDs-RGD and faded away at the 10th hour. Tumor weight and volume in PDT group,gemcitabine group and combination group were all significantly lower than those in control group and simple illumination group(P0. 05),as well as between PDT group and gemcitabine group(P >0. 05). Tumor inhibition rate in combination group,gemcitabine group and PDT group was 70. 5%,43. 5% and 37. 1%, respectively. Conclusions:QDs-RGD based PDT combined with gemcitabine can inhibit the growth of pancreatic cancer xenograft in nude mice,which introduces a new idea to the treatment of pancreatic cancer.
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.