Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Inhibitory effect of tetramethylpyrazine combined with propranolol on murine hemangioma endothelial cells

Wan-Wan Jin, Jian-Ming Wu, Yi Tong, Ji-Cong Jiang, Hehe Quan, Yu Gao

Department of Dermatology, The Second Affiliated Hospital and Yuying Childrenâ€™s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China;

For correspondence:- Yu Gao Email: ezin8s@163.com

Accepted: 28 March 2019 Published: 30 April 2019

Citation: Jin W, Wu J, Tong Y, Jiang J, Quan H, Gao Y. Inhibitory effect of tetramethylpyrazine combined with propranolol on murine hemangioma endothelial cells. Trop J Pharm Res 2019; 18(4):721-726 doi: 10.4314/tjpr.v18i4.6

© 2019 The authors.
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Abstract

Purpose: To study the inhibitory effect of different doses of tetramethylpyrazine (TMP) combined with the beta-blocker, propranolol (Pro) on hemangioma endothelial (EOMA) cells.

Methods: EOMA cells were cultured in vitro with varying doses of TMP and Pro (5, 10, 20 and 40 uM). The effect of treatments on cell proliferation was assessed by MTT assay, while cell apoptosis was assayed by flow cytometry. The expressions of Bcl-2, Bax, p-mTOR), total-mammalian target of rapamycin (t-mTOR, p-p70S6) and total-p70 ribosomal protein S6 (t-p70S6) proteins were determined using Western blot.

Results: MTT data showed that when used alone, TMP had no significant inhibitory effect on EOMA cells (p > 0.05). However, when TMP was combined with propranolol, there was significant inhibition of EOMA cells, and that the inhibition is dependent on TMP dose. Flow cytometry results showed that the combination of TMP and Pro induced EOMA cell apoptosis dose-dependently (p < 0.05). Moreover, TMP dose-dependently inhibited the phosphorylation of mTOR and p70S6 in EOMA cells, and enhanced Bax expression, but downregulated Bcl-2 (p < 0.05).

Conclusion: These results suggest that TMP enhances the inhibitory influence of Pro p-mTOR and p-p-70S6 in EOMA cells in a dose-dependent manner. Thus, TMP may enhance Pro-induced inhibition of the growth of endothelial cells, and promote apoptosis through suppression of activation of PI3K/AKT signal route. These findings provide a theoretical basis for the clinical application of TMP/Pro combination for the treatment of hemangioma.

Keywords: Hemangioma, Propranolol, Tetramethylpyrazine, Mouse hemangioma endothelial cells, Mammalian target of rapamycin, p70 ribosomal protein S6