Impact of acetylsalicylic acid on tumor angiogenesis and lymphangiogenesis through inhibition of VEGF signaling in a murine sarcoma model.

Abstract

Aspirin is a salicylate drug that is widely used, and recently it has been shown to influence the development of various types of cancers. Our previous study revealed that aspirin had an inhibitory effect on the growth of S180 sarcoma and 3AO human ovarian cancer cells. The present study utilized a murine S180 sarcoma model to investigate the molecular mechanisms involved in aspirin-induced tumor growth inhibition. Tumor-bearing mice were randomly divided into five groups with 10 mice in each group: i) control; ii) 5-fluorouracil (5-FU); iii) high-dose aspirin (250 mg/kg); iv) low-dose aspirin (50 mg/kg); and v) combination of 5-FU and aspirin (50 mg/kg). The effect of aspirin on tumor growth was observed by measuring tumor volume and evaluating the antitumor effect. Tumor histology and immunohistochemistry were performed to detect the microvessel density (MVD), lymphatic vessel density (LVD), and the expression levels of vascular endothelial growth factor A (VEGF-A) and VEGF-C. The expression of VEGF-A and VEGF-C was also confirmed and quantified by western blotting. We discovered significant growth delay in murine S180 sarcoma as a result of aspirin treatment. The inhibition rate of tumor growth induced by high-dose and low-dose aspirin was 33.5 and 22.2%, respectively (P<0.05). The expression of VEGF-A and VEGF-C in tumor tissues inhibited by aspirin was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (p<0.05). Reduced LVD was particularly apparent in the high-dose aspirin group (p<0.05). Western blot data showed that the expression of both VEGF-A and VEGF-C was reduced after treatment with aspirin. In conclusion, the impact of aspirin-induced tumor growth delay of murine S180 sarcoma may correlate with the inhibition of angiogenesis and lymphangiogenesis by reducing VEGF-A and VEGF-C expression in tumor tissues.