Hyaluronic acid modulates glioma cell proliferation through its interaction with CD44H in vitro

AbstractThe tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

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Sevoflurane Suppresses Glioma Cell Proliferation, Migration, and Invasion Both In Vitro and In Vivo Partially Via Regulating KCNQ1OT1/miR-146b-5p/STC1 Axis

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2020.3762 ◽

2020 ◽

Author(s):

Jian Wen ◽

Yan Ding ◽

Shaohua Zheng ◽

Xin Li ◽

Ying Xiao

Keyword(s):

Cell Proliferation ◽

Glioma Cell ◽

Migration And Invasion ◽

Glioma Cell Proliferation

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Correction: Retraction: Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation

Acta Pharmacologica Sinica ◽

10.1038/aps.2018.2 ◽

2018 ◽

Vol 39 (2) ◽

pp. 328-328

Keyword(s):

Cell Proliferation ◽

Glioma Cell ◽

Ros Production ◽

Ampk Activation ◽

Human Glioma ◽

Human Glioma Cell ◽

Glioma Cell Proliferation ◽

Proliferation In Vitro

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ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

Cell Death and Disease ◽

10.1038/s41419-019-1986-2 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 10

Author(s):

Xiaonan Xi ◽

Ning Liu ◽

Qianqian Wang ◽

Yahui Chu ◽

Zheng Yin ◽

...

Keyword(s):

Cell Proliferation ◽

Synergistic Effect ◽

Glioma Cell ◽

Synergistic Effects ◽

Akt Pathway ◽

Phase I Clinical Trials ◽

Glioma Cell Proliferation ◽

Pai 1

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

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