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

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

Fa Jin, Tao Xie, Xiaoguang Huang, Xinde Zhao

Pharm Biol. 2018 Dec;56(1):665-671.

PMID: 31070539

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 (IC50 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP9004324	Carboxymethylcellulose sodium		9004-32-4	Price

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