华卟啉钠介导的光动力疗法在体外和体内对肿瘤生长的抑制作用  

Inhibitory effects of DVDMS-2-based-photodynamic therapy on the growth of tumor in vitro and in vivo

作　　者：姜智换[1] 史蕤[1] 李超[2] 王爱平[2] 

机构地区：[1]中国医学科学院药物研究所,北京100050 [2]中国医学科学院北京协和医学院新药安全评价研究中心,北京100176

出　　处：《癌变．畸变．突变》2013年第3期163-167,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：科技部新药创制重大专项"十二五"平台项目(2013ZX09302302-001);中关村重大统筹项目"创新药物临床前安评基地建设"

摘　　要：目的:观察华卟啉钠(sinoporphyrin sodium,DVDMS-2)介导的光动力疗法(DVDMS-2-PDT)在体内外对肿瘤生长的抑制作用及其强度。方法:用噻唑蓝(MTT)法检测DVDMS-2在体外对4种肿瘤细胞(人肝癌细胞HepG2、人肺癌细胞H460、人胃癌细胞BGC823和人肾癌细胞Ketr-3)的生长抑制作用。采用小鼠肉瘤S180移植性肿瘤模型,按2mg/kg单次尾静脉注射给予DVDMS-2,给2药24h后进行光动力治疗,分别设低、中、高剂量照射组(分别为38、76、152J/cm),另设生理盐水阴性对照组和阳性对照组(给予210mg/kgPhotofrin,按76J/cm进行光照射),实验结束后,称瘤质量,计算各组肿瘤生长抑制率。采用裸鼠H460细胞荷瘤动物模型,设DVDMS-2低、中、高剂量组(分别为0.5、1.0、2.0mg/kg),另设生理盐水阴性对照组和阳性对照组(给予10mg/kg2Photofrin),激光照射条件为76J/cm,试验结束后,计算各组肿瘤质量、肿瘤体积、相对肿瘤增殖率T/C(%)等指标。利用SPSS13.0对数据进行统计分析。结果:DVDMS-2对HepG2、H460、BGC823和Ketr-3细胞均有明显的生长抑制作用,MTT法测定其IC值为0.207～0.584μg/mL。小鼠肉瘤S180移植性肿瘤模型抑制实验中,低、中、高剂量照射组的平均肿瘤抑制率分别为5082.83%、88.56%、95.59%,与阴性对照组比较,差异均具有统计学意义(P<0.05)。裸鼠H460细胞荷瘤动物模型中,DVDMS-20.5、1.0和2.0mg/kg对裸鼠异体移植瘤的抑制率分别为38.8%、47.9%和53.9%,与阴性对照组比较,差异均具有统计学意义(P<0.05)。结论:DVDMS-2体内外应用对肿瘤生长均有明显的抑制作用。OBJECTIVE： To observe the inhibitory effect and strength of DVDMS-2-based-photodynamic therapy （PDT） on the growth of 4 kinds of cancer cells,S180 tumor in mice and human lung cancer cell H460 in nude mice. METHODS：The antiproliferative activity of DVDMS-2 was determined by MTT method. S180 tumor model was established in mice. All 35 mice were equally divided into 5 groups randomly：the negative control group,Photofrin positive control group and DVDMS-2 with low （38 J/cm2）,medium （76 J/cm2）,high （152 J/cm2） irradiation dose groups. DVDMS-2 at doses of 2.0 mg /kg was given intravenously to mice in low,medium and high irradiation dose groups on the day 2 after implantation of S180 cells. Negative control group was given saline in same volume,and positive control group was given intravenously. Photofrin at the dose of 10 mg/kg. PDT was given at 24 h after injection. All mice were killed at day 10 after PDT,and S180 tumors were taken out to measure the weight and calculate the tumor inhibition rate. Human lung cancer cells H460 transplant model was established in nude mice. DVDMS-2 at doses of 0.5,1.0 and 2.0 mg /kg was given intravenously on the day 7 after implantation of H460.Negative control group was given saline in same volume,and positive control group was given intravenously. Photofrin at the dose of 10 mg/kg. Then mice were treated with irradiation condition 76 J/cm2 （laser 630 nm） at 24 h after injection. All mice were killed at day 5 after PDT,and H460 tumors were taken out to measure the weight and size and calculate the tumor inhibition rate and the relative tumor-suppressing rate （T/C）. Data were analyzed by SPSS software 13.0. RESULTS：Through the MTT assay,DVDMS-2-PDT could significantly inhibit the growth of cancer cells,including human hepatocellular carcinoma cells （HepG2）,human non-small lung cancer cells （H460）,human gastric cancer cells （BGC823） and human renal carcinoma cells （Ketr-3）. MTT assay showed that the IC50 toward these tumor cells was 0.20

关 键 词：华卟啉钠(DVDMS-2) PHOTOFRIN 光动力治疗 光敏剂 抗肿瘤 MTT法 

分 类 号：R73-36[医药卫生—肿瘤]