Carcinogenesis, Teratogenesis & Mutagenesis

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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

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