Evidence for the involvement of COX-2/VEGF and PTEN/Pl3K/AKT pathway the mechanism of oroxin B treated liver cancer

Abstract

Background:Oroxin B (OB) is one of flavonoids isolated from traditional Chinese herbal medicine Oroxylum indicum (L.) Vent. Recent studies suggest that flavonoids have obvious anti-liver tumors effect, but the precise molecular mechanism is still unclear.Objective:The current study was performed to investigate the antitumor effects of OB on human hepatoma cell line SMMC-772 and explore the part of molecular mechanisms in this process.Materials and Methods:MTT method, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry were utilized to detect the inhibition of proliferation and the apoptosis after treating OB in of SMMC-7721 cells. The mRNA and proteins expressions of COX-2, vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase (PI3K), p-AKT, and PTEN were measured by a real-time polymerase chain reaction and Western Blot method.Results:The results showed that OB inhibited proliferation of SMMC-7721 cell in a dose-dependent manner, and induced its apoptosis. Moreover, OB unregulated PTEN and downregulated COX-2, VEGF, p-AKT, and PI3K.Conclusion:Our results demonstrated that OB significantly inhibits proliferation and induce apoptosis, which may be strongly associated with the inhibiting COX-2/VEGF and PTEN/PI3K/AKT pathway signaling pathway in SMMC-7721 cells, OB potentially be used as a novel therapeutic agent for liver cancer.SUMMARY OB (Oroxin B) is one of the effective flavonoid components of traditional Chinese medicine O. indicum (L.)OB can inhibite the proliferation and promoted apoptosis of the human hepatoma cell line SMMC 7721OB plays a role of antitumor effect may to regulate COX 2/VEGF and PTEN/PI3K/AKT pathways directly or indirectly. Abbreviations used: OB: Oroxin B; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; COX-2: cyclooxygenase-2; PI3K: phosphatidylinositol 3 kinase; PTEN: Phosphatase and tensin homolog deleted on chromosome ten; VEGF: Vascular endothelial growth factor; RT-PCR: Reverse transcription polymerase chain reaction; DAPI: Diamidino 2 phenylindole; PBS: Phosphate buffer saline; FITC: Fluorescein isothiocyanate; PI: Propidium Iodide; RIPA: Radio immunoprecipitation assay lysis buffer; PMSF: Phenylmethanesulfonyl fluoride; PAGE: Polyacrylamide gel electrophoresis.

Phytochemicals Targeting VEGF and VEGF-Related Multifactors as Anticancer Therapy

“…Oroxin B, a flavone glycoside isolated from this plant, suppresses proliferation of liver cancer cells. Furthermore, it suppresses COX-2/VEGF and PTEN/PI3K/Akt signaling pathways [91].…”

Mir526b and Mir655 Promote Tumour Associated Angiogenesis and Lymphangiogenesis in Breast Cancer

“…PTEN is also a known target of other established miRNAs, such as miR-494, which has been reported by Mao et al to target PTEN in response to hypoxic conditions to promote angiogenesis and tumour growth in non-small lung cancer [36]. PTEN acts as a tumour suppressor gene both by inhibiting the PI3K/Akt pathway, and by acting as a negative regulator of HIF-1α (hypoxia-inducible factor-1) [38,39]. In turn, HIF-1α is a transcription factor known to promote the transcription of many angiogenesis-associated genes, including VEGFs [40].…”

Circular RNA-9119 suppresses in ovarian cancer cell viability via targeting the microRNA-21-5p–PTEN–Akt pathway

“…Oroxin B (OB), a PTEN agonist (SMB00340, Sigma), was used to promote PTEN activity and inhibit Akt phosphorylation [ 27 ]. The cells were incubated with 5 μM OB for 12 h.…”