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LGR6通过激活Akt信号通路促进胶质母细胞瘤的恶性进展和化疗耐药性。

LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway.

作者信息

Cheng Yuan Yuan, Yang Xue, Gao Xin, Song Si Xin, Yang Ming Feng, Xie Fang Min

机构信息

Department of Oncology, Tai'an Central Hospital, Tai'an, Shandong 271000, P.R. China.

Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China.

出版信息

Exp Ther Med. 2021 Dec;22(6):1364. doi: 10.3892/etm.2021.10798. Epub 2021 Sep 27.

Abstract

Chemoresistance is the primary cause of the poor outcome of glioblastoma multiforme (GBM) therapy. Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) is involved in the growth and proliferation of several types of cancer, including gastric cancer and ovarian cancer. Therefore, the aim of the present study was to investigate the role of LGR6 in GBM malignancy and chemoresistance. Cell counting kit-8 and Matrigel-Transwell assays were conducted to assess GBM cell viability and invasion. The effect of LGR6 on cell cycle progression and activation of Akt signaling was analyzed by performing propidium iodide staining and western blotting, respectively. The results demonstrated that LGR6, a microRNA-1236-3p target candidate, promoted GBM cell viability and invasion, and mediated temozolomide sensitivity in SHG-44 and U251 GBM cells. In addition, LGR6 triggered the activation of the Akt signaling pathway during GBM progression. Collectively, the results of the present study suggested that LGR6 promoted GBM malignancy and chemoresistance, at least in part, by activating the Akt signaling pathway. The results may aid with the identification of a novel therapeutic target and strategy for GBM.

摘要

化疗耐药是多形性胶质母细胞瘤(GBM)治疗效果不佳的主要原因。富含亮氨酸重复序列的G蛋白偶联受体6(LGR6)参与包括胃癌和卵巢癌在内的多种癌症的生长和增殖。因此,本研究的目的是探讨LGR6在GBM恶性肿瘤和化疗耐药中的作用。进行细胞计数试剂盒-8和基质胶Transwell试验以评估GBM细胞活力和侵袭能力。分别通过碘化丙啶染色和蛋白质印迹法分析LGR6对细胞周期进程和Akt信号通路激活的影响。结果表明,作为微小RNA-1236-3p的候选靶标,LGR6促进GBM细胞活力和侵袭,并介导替莫唑胺对SHG-44和U251 GBM细胞的敏感性。此外,LGR6在GBM进展过程中触发Akt信号通路的激活。总体而言,本研究结果表明,LGR6至少部分通过激活Akt信号通路促进GBM恶性肿瘤和化疗耐药。这些结果可能有助于确定GBM的新型治疗靶点和策略。

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