Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7775-81. eCollection 2014.

Abstract

Aim: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model.

Methods: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry.

Results: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment.

Conclusion: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC.

Keywords: Hepatocellular carcinoma; MVD; TACE; VEGF; sorafenib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Disease Models, Animal
  • Injections, Intra-Arterial
  • Iodized Oil / administration & dosage
  • Iodized Oil / therapeutic use*
  • Liver / blood supply*
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / therapeutic use*
  • Rabbits
  • Sorafenib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Iodized Oil
  • Sorafenib