Berberine Inhibits Angiogenesis in Glioblastoma Xenografts by Targeting the VEGFR2/ERK Pathway

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2019 May 10

PMID 31070539

Citations 28

Authors

Fa Jin

Tao Xie

Xiaoguang Huang

Xinde Zhao

Affiliations

Soon will be listed here.

Abstract

Context: Berberine is used in traditional Chinese medicine for thousands of years with recent reports of its anticancer activity.

Objective: To test antiangiogenic effects of berberine on human glioblastoma and clarify involvement of the VEGFR2/ERK pathway.

Materials And Methods: Cell viability, proliferation and migration assays were performed to determine in vitro antiangiogenic effects of berberine (6.25-200 μmol/L, 6-48 h). Ectopic and orthotopic xenograft models in BALB/c nude mice were induced to determine antitumour and antiangiogenic effects of berberine (50 mg/kg by oral gavage for 28 days) or vehicle control (carboxymethylcellulose sodium).

Results: Berberine inhibited cell viability (IC of 42 and 32 μmol/L, respectively) and proliferation of U87 and U251 human glioblastoma cell lines. Berberine (50 μmol/L) inhibited cell migration of HUVEC by 67.50 ± 8.14% in the Transwell assay and tube formation of HUVEC by 73.00 ± 11.12% in the Matrigel assay. In the ectopic xenograft model, tumour weight was significantly decreased by 50 mg/kg of berberine (401.2 ± 71.5 mg vs. 860.7 ± 117.1 mg in vehicle group, p ˂ 0.001). Berberine significantly decreased haemoglobin content (28.81 ± 3.64 μg/mg vs. 40.84 ± 5.15 μg/mg in vehicle group, p ˂ 0.001) and CD31 mRNA expression in tumour tissue. In the orthotopic xenograft model, berberine (50 mg/kg) significantly improved the survival rate of mice (p = 0.0078). Berberine inhibited (p ˂ 0.001) the phosphorylation of VEGFR2 and ERK.

Discussion And Conclusions: Berberine inhibited angiogenesis in glioblastoma xenografts by targeting the VEGFR2/ERK pathway. Our work sheds new light on complementary and alternative therapy for glioblastoma.

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