Scutellarin inhibits human renal cancer cell proliferation and migration via upregulation of PTEN - 20/09/18
, Wei Han b, Tao Fan a, Xiaoku Wang a, Zhao Cheng a, Bo Wan a, Jinlian Chen aBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Graphical abstract |
Highlights |
• | Scutellarin inhibites RCC cell proliferation in dose- and time- dependent manner. |
• | Scutellarin induces apoptosis and cell cycle arrested at G0/G1 phase. |
• | Cell invasion and migration capacities of RCC cells are suppressed by Scutellarin. |
• | Scutellarin possesses anti-cancer effect on xenograft without toxic effect. |
• | Scutellarin increases PTEN and inhibits P13K/AKT/mTOR activation in RCC cells. |
Abstract |
Background |
Scutellarin is a naturally flavone glycoside that has been shown to exhibit anti-proliferative and anti-apoptotic activities among various human malignancies. However, the anti-cancer effect of Scutellarin in Renal cell carcinoma (RCC) and the underlying mechanism remains unclear.
Methods and materials |
RCC cell lines ACHN and 786-O were treated with different concentrations (0–210 μM) of Scutellarin in vitro. Cell viability and proliferation were investigated by MTT and colony formation assays. Cell invasion and migration were detected by Transwell assays. Cell apoptosis and cell cycle distribution was measured by flow cytometry. Western blot was used to investigate the expression levels of crucial proteins. Xenograft tumor model was established to evaluate tumor growth in vivo.
Results |
Scutellarin significantly inhibited RCC cell proliferation in a dose- and time- dependent manner. Treatment of RCC cells with Scutellarin (30, 60, and 90 μM) markedly induced apoptosis and cell cycle arrested at G0/G1 phase in a concentration-dependent characteristic. Cell invasion and migration capacities of RCC cells were also dose-dependently suppressed by Scutellarin treatment. Western blot assays revealed that the crucial proteins including cyclin D1, CDK2, Bcl2, MMP-2, and MMP-9 were significantly reduced while Bax, cleaved caspase 3 and p21 were increased by Scutellarin in RCC cells. In vivo assay indicated that Scutellarin possessed anti-cancer effect on xenograft without triggering toxic effect. Mechanically, Scutellarin dramatically increased the protein level of phosphatase and tensin homologue (PTEN) and inhibited the activity of P13K/AKT/mTOR signaling. Ectopic expression of PTEN enhanced the inhibitory effect of Scutellarin on RCC proliferation while knockdown of PTEN abrogated it through regulating its downstream P13K/AKT/mTOR signaling pathway.
Conclusion |
Scutellarin inhibited RCC cell proliferation and invasion partially by enhancing the expression of PTEN through inhibition of P13K/AKT/mTOR pathway, suggesting that Scutellarin might serve as a potential therapeutic agent in RCC treatment.
El texto completo de este artículo está disponible en PDF.Keywords : Scutellarin, Renal cancer, PTEN, P13K/AKT/mTOR, Proliferation
Esquema
Vol 107
P. 1505-1513 - novembre 2018 Regresar al número
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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