Microwave ablation combined with attenuated Salmonella typhimurium for treating hepatocellular carcinoma in a rat model

Oncotarget. 2017 Jul 18;8(29):47655-47664. doi: 10.18632/oncotarget.17468.

Abstract

We aim to investigate the safety and efficacy of microwave ablation (MWA) combined with attenuated Salmonella typhimurium strain VNP20009 in treating hepatocellular carcinoma. Portions of tumor tissues were orthotopically implanted in the livers of 40 male rats weighed 150~200 g to establish tumor models. Three weeks later, the rats were randomly divided into four groups: (A) MWA plus VNP20009 group; (B) MWA group; (C) VNP20009 group; and (D) control group. Incomplete MWA was performed (20~30 W, 1~2 min) after the hepatic carcinoma was properly exposed. VNP20009 (about 1×107 cfu) was directly injected into the tumor immediately. MRI scans were performed to assess the tumor responses 7 and 14 days later, respectively. Micro CT was used to observe the lung metastases. After the animals were sacrificed or died, the tumors were cut off for the purpose of pathological and immunohistochemical analyses. The results showed that the mean tumor volumes of MWA plus VNP20009 group on the 7th and 14th day post treatment were obviously smaller than those of other groups (P < 0.05). Lung metastases rates were 20%, 60%, 30% and 100% in MWA plus VNP20009 group, MWA group, VNP20009 group and control group, respectively. The median survival of the rats in MWA plus VNP20009 group was distinctly longer than those in other groups (P < 0.05). In summary, MWA combined with VNP20009 produced better effects than MWA or VNP20009 alone in treating hepatic carcinoma. This strategy might have potential ability to decrease lung metastases and prolong the overall survival.

Keywords: VNP 20009; hepatocellular carcinoma; microwave ablation.

MeSH terms

  • Ablation Techniques*
  • Animals
  • Apoptosis
  • Biomarkers
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Combined Modality Therapy
  • Disease Models, Animal
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / therapy*
  • Magnetic Resonance Imaging
  • Male
  • Microwaves* / therapeutic use
  • Neoplasm Metastasis
  • Rats
  • Salmonella typhimurium*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers