title: Sonodynamically induced anti-tumor effect with protoporphyrin IX on hepatoma-22 solid tumor.
abstract: OBJECTIVE
  The purpose of this study was to evaluate sonodynamically induced anti-tumor effect of protoporphyrin IX (PPIX) in mice bearing hepatoma-22 (H-22) solid tumors, and the possible in vivo cell damage mechanism was also investigated.
  
  
  METHODS
  The pharmacokinetics of PPIX was analyzed in plasma, skin, muscle and tumor of H-22 bearing mice. Tumors were irradiated with ultrasound (1.43MHz, I(SATA) 3W/cm(2), 3min) for three times at 8, 12 and 24h after 5.0mg/kg PPIX administration, respectively. The anti-tumor effects of sonodynamic therapy (SDT) were estimated by the tumor inhibition ratio (volume and weight). The bio-effects of SDT were evaluated by hematoxylin and eosin (H&E) staining, transmission electron microscope (TEM) observation, lipid peroxidation (LPO) measurement and anti-oxidative enzymes (glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD)) assay.
  
  
  RESULTS
  A significant anti-tumor effect was obtained by PPIX-mediated sonodynamic therapy (PPIX-SDT). At the fifteenth day after PPIX-SDT, the tumor growth and tumor weight inhibition ratios were 53.84% and 45.86%, respectively. In addition, the structure of tumor tissues and the anti-oxidative enzymes were obviously destroyed after SDT treatment.
  
  
  CONCLUSIONS
  A biochemical mechanism was involved in PPIX-SDT in vivo, and the free radicals produced by the synergistic treatment destroying the anti-oxidative system of tumor cells in vivo may play an important role in this action. Also, the thermal effect could not be excluded in inducing damage of cellular structures, like membrane disruption and chromatin condensation under current evaluation in this paper.
authors.affiliation: Key Laboratory of Ministry of Education for Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Cheng
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D011524:Protoporphyrins / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C028025:protoporphyrin IX