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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

姜智换1,史 蕤1,*,李 超2,王爱平2,*   

  1. ( 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 )
  • 收稿日期:2013-01-31 修回日期:2013-04-18 出版日期:2013-05-30 发布日期:2013-05-30
  • 通讯作者: 姜智换 jnkic@163.com
  • 作者简介:姜智换 (1987- ),女 ,河北省沧州市人,硕士,研究方向:药理毒理学。E-mail:jnkic@163.com
  • 基金资助:

    科技部新药创制重大专项“十二五”平台项目 (2013ZX0930 2302- 001),中关村重大统筹项目“创新药物临床前安评基地建设”

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

JIANG Zhi-huan1,SHI Rui1,*,LI Chao2,WANG Ai-ping2,*   

  1. (1. Institute of Materia Medica, Chinese Academy of MedicalSciences, Beijing 100050; 2.New Drug Safety Evaluation Center in Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China)
  • Received:2013-01-31 Revised:2013-04-18 Online:2013-05-30 Published:2013-05-30
  • Contact: JIANG Zhi-huan jnkic@163.com

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2 mg/kg单次尾静脉注射给予DVDMS-2,给药24 h后进行光动力治疗,分别设低、中、高剂量照射组 (分别为38、76、152 J/cm2),另设生理盐水阴性对照组和阳性对照组 (给予10 mg/kg Photofrin,按76 J/cm2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、2.0 mg/kg),另设生理盐水阴性对照组和阳性对照组 (给予10 mg/kg Photofrin),激光照射条件为76 J/cm2 ,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SPSS 13.0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IC50值为0.207~0.584 μg/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82.83%、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-2 0.5、1.0和2.0 mg/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。

 

关键词: 华卟啉钠 (DVDMS-2), Photofrin, 光动力治疗, 光敏剂, 抗肿瘤, MTT法

Abstract:

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 0.207-0.584 μg/mL. In the mouse model of S180 tumor,the tumor weight inhibition rates treated under irradiation condition (38,76,152 J/cm2) 24 h after DVDMS-2 (2 mg/kg) injection were 82.83%,88.56%,95.59% (P<0.05),respectively. In human lung cancer cell H460 in nude mice,the tumor weight inhibition rates treated with DVDMS-2 (0.5,1,2 mg/kg) were 38.8%,47.9% and 53.9% (P<0.05),respectively,under the irradiation condition of 76 J/cm2. CONCLUSION:DVDMS-2-PDT showed significant antitumor activities in vitro and in vivo.

Key words: DVDMS-2, Photofrin, photodynamic therapy, photosensitizer, antitumor, MTT assay