Abstract 1296: Vascular shutdown anti-tumor effect of tetra-arsenic oxide on cervical cancer cells

Abstract

Abstract Background: Tetra arsenic oxide (As4O6) is a novel arsenic compound that exhibits potent anti-vascular activity and significantly suppresses solid tumor growth. The present study was conducted to investigate the vascular shutdown effects in HPV E6/E7-expressing tumors bearing mice. Methods: After tumors reached 300-350 mm3 in volume, mice were randomly divided into four groups and treated intraperitoneally with three different dose of As4O6 at 1-week interval. Tumor blood perfusion and vascularity were visualized using Hoechst 33342, CD31 staining respectively from 1 hour to 1 week after As4O6 treatment. Histopathological features were observed following hematoxylin and eosin staining. Apoptosis, TNF-a, caspase activity and tumor regression were used to determine the mechanisms for vascular shutdown effects. Results: As4O6 significantly suppressed tumor growth compared with control group. This tumor growth inhibition led to massive necrosis and vascular shutdown in tumor tissue, and also tumor tissue necrosis and apoptosis. Mice treated with As4O6 had a reduction in tumor vessel dimensions compared with the control animals, with CD31 stained microvessels still being apparent at the outer edge of the tumor. Additionally, in the control group, vessel area and diameter increased over time, whereas in the tumors from the As4O6-treated group, vessel area and diameter remained stable or decreased. Apoptotic cell populations induced by As4O6 were increased by double staining the TC-1 cells with annexin V and propidium iodide. Conclusions: The results suggest that As4O6 has potential anticancer activity that is exerted by vascular shutdown in C57BL/6 mice transplanted with TC-1 cells. The study is novel in the observation of recovery of disturbed vascular function. Citation Format: Yong-Wan Kim. Vascular shutdown anti-tumor effect of tetra-arsenic oxide on cervical cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1296.