Bo Yu1, Wei Liu1, Min-Qi Hu1, Xiu-Fa Tang1, Chun-Jie Li1, Lin Que1. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Abstract
OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS: B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS: B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
Authors: Dirk Schadendorf; Alexander C J van Akkooi; Carola Berking; Klaus G Griewank; Ralf Gutzmer; Axel Hauschild; Andreas Stang; Alexander Roesch; Selma Ugurel Journal: Lancet Date: 2018-09-15 Impact factor: 79.321
Authors: Kimberly D Miller; Leticia Nogueira; Angela B Mariotto; Julia H Rowland; K Robin Yabroff; Catherine M Alfano; Ahmedin Jemal; Joan L Kramer; Rebecca L Siegel Journal: CA Cancer J Clin Date: 2019-06-11 Impact factor: 508.702
Authors: Georgina V Long; Axel Hauschild; Mario Santinami; Victoria Atkinson; Mario Mandalà; Vanna Chiarion-Sileni; James Larkin; Marta Nyakas; Caroline Dutriaux; Andrew Haydon; Caroline Robert; Laurent Mortier; Jacob Schachter; Dirk Schadendorf; Thierry Lesimple; Ruth Plummer; Ran Ji; Pingkuan Zhang; Bijoyesh Mookerjee; Jeff Legos; Richard Kefford; Reinhard Dummer; John M Kirkwood Journal: N Engl J Med Date: 2017-09-10 Impact factor: 91.245