Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on lymphangiogenesis of gastric cancer in a nude mouse model

Abstract

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) can inhibit tumor growth by inhibition of angiogenesis. This study was designed to study the anticancer effects of ACEI and ARB on tumor growth and lymphangiogenesis in an implanted gastric cancer mouse model. A model of gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901 into 60 nude mice. One week later, all mice were randomly divided into 5 groups. A control group received physiologic saline once daily for 21 days. Mice in the 4 treatment groups received one of the following agents by gavage once daily for 21 days: perindopril, 2 mg/kg; captopril, 5 mg/kg; losartan, 50 mg/kg; or valsartan, 40 mg/kg. Twenty-one days after treatment, all the mice were sacrificed and the tumors were removed. Tumor sections were processed, and immunohistochemical methods were used to observe the expressions of vascular endothelial growth factor C (VEGF-C), matrix metalloproteinase 7 (MMP-7), and lymphatic microvessel density (LMVD). Tumor volume was significantly inhibited in all ACEI and ARB groups, compared with the control group (all P < 0.01). LMVD in the ACEI and ARB groups was also significantly lower than that of the control group (all P < 0.01). In the ACEI groups, the expressions of VEGF-C and MMP-7 were both significantly decreased, compared with the control group (all P < 0.05). In the ARB groups, expression of VEGF-C was significantly decreased compared with the control group (all P < 0.05). However, no significant difference was found in the expression of MMP-7 between ARB groups and the control group. In a mouse model, ACEI and ARB might inhibit gastric cancer tumor growth by suppressing lymphangiogenesis.