Department of Ultrasonic Imaging, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Department of Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Life Sci. 2020 Oct 1;258:118158. doi: 10.1016/j.lfs.2020.118158. Epub 2020 Aug 1.
Glioblastoma multiforme (GBM) is characterized by aggressive infiltration and terrible lethality. The overwhelming majority of chemotherapeutic drugs fail to exhibit the desired treatment effects. Polydatin (PD), which was initially extracted from Polygonum cuspidatum, is distinguished for its outstanding cardioprotective, hepatoprotective, and renal protective effects, as well as significant anticancer activities. However, the anti-GBM effect of PD is unclear.
Cell proliferation and apoptosis after PD intervention were estimated using MTT, colony formation and flow cytometry assays in vitro, while wound-healing and Transwell assays were applied to assess cell migration and invasion. In addition, the anti-GBM effects of PD in vivo were detected in the subcutaneous tumor model of nude mice. Moreover, Western blot, immunofluorescence and immunohistochemical staining assays were employed to elaborate the relevant molecular mechanisms.
The present study demonstrated that PD repressed cell proliferation, migration, invasion and stemness and promoted apoptosis in GBM cells. Moreover, by correlating the molecular characteristics of cancer cells with different sensitivities to PD and employing diverse analytical methods, we ultimately verified that the cytotoxicity of PD was related to EGFR-AKT/ERK1/2/STAT3-SOX2/Snail signaling pathway inhibition, in which multiple components were vital therapeutic targets of GBM.
This work demonstrated that PD could inhibit proliferation, migration, invasion and stemness and induce apoptosis by restraining multiple components of the EGFR-AKT/ERK1/2/STAT3-SOX2/Snail signaling pathway in GBM cells.
多形性胶质母细胞瘤（GBM）的侵袭性强，致死率高。绝大多数化疗药物未能达到理想的治疗效果。虎杖苷（PD）最初从虎杖中提取，具有突出的心脏保护、肝脏保护和肾脏保护作用以及显著的抗癌活性。然而，PD 对 GBM 的作用尚不清楚。
通过 MTT、集落形成和流式细胞术检测 PD 干预后细胞增殖和凋亡，通过划痕愈合和 Transwell 检测评估细胞迁移和侵袭。此外，在裸鼠皮下肿瘤模型中检测 PD 的抗 GBM 作用。还采用 Western blot、免疫荧光和免疫组化染色检测来阐述相关的分子机制。
本研究表明 PD 抑制 GBM 细胞的增殖、迁移、侵袭和干性，并促进其凋亡。此外，通过将癌细胞的分子特征与 PD 的不同敏感性相关联，并采用不同的分析方法，最终验证了 PD 的细胞毒性与 EGFR-AKT/ERK1/2/STAT3-SOX2/Snail 信号通路抑制有关，其中多个成分是 GBM 的重要治疗靶点。
本研究表明 PD 可通过抑制 EGFR-AKT/ERK1/2/STAT3-SOX2/Snail 信号通路中的多个成分，抑制 GBM 细胞的增殖、迁移、侵袭和干性，并诱导其凋亡。
