Wang Bin, Li Jingyu
Third Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Department of Ultrasonography, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Cancer Manag Res. 2020 Apr 20;12:2631-2640. doi: 10.2147/CMAR.S238173. eCollection 2020.
Piceatannol (PIC) is confirmed to inhibit the proliferation of various tumors, but its role in osteosarcoma still remains unknown. This study investigated the function of PIC in osteosarcoma, aiming to provide a research basis for osteosarcoma therapy.
Human osteosarcoma cells in this study were, respectively, treated with PIC at various concentrations (0, 20, 40, 80 μmol/L), PI3K/AKT/mTOR pathway inhibitor (LY294002), or pathway activator (740Y-P) plus PIC. Osteosarcoma cells were subcutaneously injected into nude mice to establish xenograft models, and PIC was intraperitoneally injected into models. The activity, proliferation, apoptosis and cell cycle of treated cells were determined by MTT test, colony formation assay or a flow cytometry. The expressions of PI3K/AKT/mTOR pathway-related proteins in cells and tumor tissues were measured by Western blot (WB) analysis.
PIC (40 and 80 μmol/L) and LY294002 availably suppressed activity and proliferation and induced apoptosis of osteosarcoma cells. PIC observably increased the number of cells retarded in G2 phase, but decreased the cell percentages in G1 and S phases. Conversely, 740Y-P reversed the effects of PIC on osteosarcoma cells, which promoted cell activity and proliferation and restrained apoptosis. In xenograft models, the volume and weight of the tumors treated by PIC were visibly alleviated than those untreated. The PI3K/AKT/mTOR pathway was prominently inhibited in PIC-treated osteosarcoma cells and tumor tissues.
PIC suppresses the proliferation and induces apoptosis of osteosarcoma cells through regulating PI3K/AKT/mTOR pathway, which is expected to be the therapeutic of osteosarcoma.
已证实白皮杉醇（PIC）可抑制多种肿瘤的增殖，但其在骨肉瘤中的作用仍不清楚。本研究旨在探讨PIC在骨肉瘤中的功能，为骨肉瘤治疗提供研究依据。
本研究中，人骨肉瘤细胞分别用不同浓度（0、20、40、80μmol/L）的PIC、PI3K/AKT/mTOR通路抑制剂（LY294002）或通路激活剂（740Y-P）加PIC处理。将骨肉瘤细胞皮下注射到裸鼠体内建立异种移植模型，并对模型腹腔注射PIC。通过MTT试验、集落形成试验或流式细胞术测定处理后细胞的活性、增殖、凋亡和细胞周期。通过蛋白质免疫印迹（WB）分析测定细胞和肿瘤组织中PI3K/AKT/mTOR通路相关蛋白的表达。
PIC（40和80μmol/L）和LY294002可有效抑制骨肉瘤细胞的活性和增殖并诱导其凋亡。PIC明显增加了阻滞在G2期细胞的数量，但降低了G1期和S期细胞的百分比。相反，740Y-P逆转了PIC对骨肉瘤细胞的作用，促进了细胞活性和增殖并抑制了凋亡。在异种移植模型中，PIC处理的肿瘤体积和重量比未处理的明显减轻。在PIC处理的骨肉瘤细胞和肿瘤组织中，PI3K/AKT/mTOR通路受到显著抑制。
PIC通过调节PI3K/AKT/mTOR通路抑制骨肉瘤细胞的增殖并诱导其凋亡，有望成为骨肉瘤的治疗方法。
