Abstract 3707: Captopril inhibits colorectal cancer liver metastases following 70% partial hepatectomy in a mouse model

Abstract

Abstract Background: Blockade of the renin-angiotensin system (RAS) with the angiotensin-converting enzyme inhibitor, Captopril, has been shown to inhibit CRCLM. Partial hepatectomy (PH) for colorectal cancer liver metastases (CRCLM) can stimulate tumour recurrence. Aim: This study investigated the effects of Captopril on liver regeneration (LR), as well as on CRCLM in the regenerating liver. Methods: Male CBA mice were used for 70% PH as well as 70% PH following CRCLM induction. Mice were randomly assigned to control or Captopril-treated groups. Liver and tumour samples were collected on days 1, 2, 4, 6 and 8, 16 and 21 post-surgery. The rate of LR was measured by liver-to-body weight (LBW) ratio. The percentage of liver metastases was quantified using quantitative stereology and immunohistochemistry was performed to quantify hepatocyte and tumour cell proliferation (anti-Ki67) and apoptosis (anti-caspase-3). Results: Captopril increased LBW (0.57 ± 0.02 Captopril, 0.49 ± 0.02 control, p = 0.027) compared to controls on day 2 following 70% PH. At day 6, Captopril had decreased LBW (0.5 ± 0.03, 0.73 ± 0.06, p = 0.006). However, by day 8, LBW was not different between the control and Captopril groups. At day 21, Captopril decreased the percentage of liver metastases compared to controls (24.4 ± 6.2%; 48.7 ± 4.7%, p = 0.008) in the regenerating liver. Tumour volume (388.3 ± 150.4; 1046.2 ± 200.2mm3, p = 0.02) and tumour nodule count per image field (68 ± 17.6; 181.1 ± 28.5, p = 0.005) were also decreased by Captopril. In contrary, Captopril did not significantly alter liver volume compared to controls (886.1 ± 65.2; 1044.1 ± 115.8, p = 0.254). Furthermore, LBW during LR in the presence of CRCLM at day 2 (0.53 ± 0.01; 0.51 ± 0.02, p = 0.449) and day 6 (0.71 ± 0.01; 0.73 ± 0.03, p = 0.51) were not different between Captopril and control groups. Conclusion: Captopril enhanced the early stage of LR following 70% PH. Captopril inhibits CRCLM in the regenerating liver without inhibiting LR. Understanding the mechanisms of actions of Captopril is required to improve CRCLM patient outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3707. doi:1538-7445.AM2012-3707