Efficacy of Electrochemotherapy with Bleomycin, Oxaliplatin, or Oxaliplatin with Bevacizumab in the Treatment of Colorectal Hepatic Metastases in Rats

Abstract

Background/Objectives: Electrochemotherapy (ECT) has been shown to be effective in treating colorectal liver metastases when combined with bleomycin (BLM). Based on this promising finding, we compared in this study the efficacy of BLM with oxaliplatin (OXP) and bevacizumab (BVZ) in ECT. Methods: WAG/Rij rats were randomized into three groups and underwent ECT with intravenous injection of BLM, OXP, or OXP with BVZ for eight days following hepatic tumor cell implantation. Ultrasound and photoacoustic imaging served to assess oxygen saturation (SO2) and hemoglobin concentration (HbT) of the developing tumors. Tissue samples were analyzed by histology and immunohis tochemistry. Results: BLM treatment significantly reduced SO2 (33.7%) and HbT (12.7%) levels compared to pretreatment values. In contrast, the OXP-treated groups exhibited only modest reductions in both parameters. BLM also induced a markedly higher necrosis rate (82.6%) compared to OXP and OXP/BVZ (11.0% and 26.3%). Conversely, OXP-treated tumors exhibited higher apoptosis rates. Furthermore, BLM treatment led to a decrease in tumor cell proliferation and a reduction in inflammatory response compared to the other treatments. Notably, BLM caused a 26.2% reduction in CD31-positive microvessels, which was significantly higher than that observed in the OXP group. Conclusions: BLM showed a more effective anti-tumor activity than OXP, suggesting its preferred use as chemotherapeutic agent in ECT.