Abstract
To investigate the effects of ASMase mediated endothelial cell apoptosis in multiple hypofractionated irradiations in CT26 tumor bearing mice. Thirty-five CT26 tumor bearing mice were subjected to single ionizing radiation (IR) of 0, 3, 6, 9, 12, 15, 18 Gy. Eight hours after IR, the mice were sacrificed and tumor tissues were used for CD31 immunohistochemistry staining, TUNEL and CD31 double staining, ASMase activity assay. Then 6 and 12 Gy were chosen for multiple hypofractionated IR experiments according to the above results. Each time after IR, 5 mice were sacrificed and assayed as above. The ASMase activities were increased significantly after a single IR of 12 Gy or higher which was accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. For 6 Gy which was not high enough to trigger ASMase activation, after 2 or more times of IR, the ASMase activities were significantly increased accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. While for 12 Gy, after 2 or more times of IR, the ASMase activities and endothelial cell apoptosis rates were maintained without remarkable increase; however, the MVD was significantly decreased. What's more, the cancer cell apoptosis rates were significantly increased after multiple IR for both 6 Gy and 12 Gy. ASMase mediated endothelial cell apoptosis may play an important role in the process of multiple hypofractionated IR for CT26 colorectal carcinoma.
Highlights
DNA has been considered as the main cellular target of deleterious effects of ionizing radiation (IR) (Pollard and Gatti, 2009)
ASMase mediated endothelial cell apoptosis may play an important role in the process of multiple hypofractionated IR for CT26 colorectal carcinoma
ASMase activation is implicated in lung development (Longo et al, 1997), in the signaling of stress responses to bacteria and viruses (Utermohlen et al, 2003), and in the apoptotic response of endothelial cells to IR (Garcia-Barros et al, 2003), to UV light (Zhang et al, 2001), and to chemotherapeutic drugs (DimancheBoitrel et al, 2005)
Summary
DNA has been considered as the main cellular target of deleterious effects of ionizing radiation (IR) (Pollard and Gatti, 2009). Many investigations demonstrated that radiation doses higher than 8-10 Gy induces rapid apoptosis of tumor vascular endothelial cells by activating ASMase (Park et al, 2012; Lan et al, 2013), leading to secondary death in tumor cells. This effect was further confirmed in microvascular endothelium in lung, brain and small intestines (Pena et al, 2000; Li et al, 2003; Rotolo et al, 2008; Corre et al, 2010; Hua and Kolesnick, 2013). It’s very important to investigate the effects of ASMase mediated endothelial cell apoptosis in multiple hypofractionated IR
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