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紫甘薯矢车菊素-3-芦丁通过诱导miR-20b-5p/Atg7依赖性细胞静止自噬抑制胶质瘤增殖。

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy.

作者信息

Wang Meng, Liu Ke, Bu Huimin, Cong Hao, Dong Guokai, Xu Nana, Li Changgen, Zhao Yunyun, Jiang Fei, Zhang Yongjing, Yuan Bo, Li Rongpeng, Jiang Jihong

机构信息

Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, People's Republic of China.

Public Experimental Research Center, Xuzhou Medical University, Xuzhou, Jiangsu 221004, People's Republic of China.

出版信息

Mol Ther Oncolytics. 2022 Jul 31;26:314-329. doi: 10.1016/j.omto.2022.07.007. eCollection 2022 Sep 15.

Abstract

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both and . Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation . In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

摘要

胶质瘤是最常见的原发性颅内恶性肿瘤。由于其具有高度侵袭性和转移性,即使进行手术、放疗和化疗,该疾病的预后仍然很差。芦丁是一种糖苷类天然黄酮,可调节小胶质细胞炎症特征并增强抗胶质瘤活性。在此,提取了一种糖苷类黄酮并将其命名为紫甘薯飞燕草素 -3-芦丁(PSPD3R)。在一项使用人胶质母细胞瘤(GBM)皮下异种移植模型和alamar蓝测定法的实验中,我们发现PSPD3R在体内和体外均抑制了胶质瘤的增殖。流式细胞术测定和透射电子显微镜观察显示,PSPD3R刺激了胶质瘤细胞的自噬和凋亡。高通量微小RNA(miRNA)测序表明,PSPD3R显著影响U251细胞的miRNA表达。吖啶橙染色和免疫印迹表明,PSPD3R通过Akt/Creb/miR-20b-5p在胶质瘤细胞中调节自噬。荧光素酶报告基因测定表明,自噬相关基因7(Atg7)mRNA是miR-20b-

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b55/9420429/e2398f9ca32e/fx1.jpg

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