Doxorubicin hydrochloric increases tumour coagulation and end-point survival in percutaneous microwave ablation of tumours in a VX2 rabbit tumour model

Int J Hyperthermia. 2016 May;32(3):265-71. doi: 10.3109/02656736.2015.1137639. Epub 2016 Feb 24.

Abstract

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually.

Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment.

Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 4.08 cm(2) ± 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 1.69 cm(2) ± 0.34 cm(2), respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p < 0.01) or the DOX group (mean 35.17 days ± 7.63, p < 0.01).

Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.

Keywords: Breast cancer; VX2; microwave ablation; neoadjuvant chemotherapy.

MeSH terms

  • Ablation Techniques*
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Doxorubicin / administration & dosage*
  • Doxorubicin / therapeutic use
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Microwaves*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / surgery*
  • Rabbits

Substances

  • Antibiotics, Antineoplastic
  • HSP70 Heat-Shock Proteins
  • Doxorubicin
  • Caspase 3