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槲皮素通过抑制糖酵解代谢抑制神经胶质瘤生长并延长存活率。

Quercetin Inhibits Glioblastoma Growth and Prolongs Survival Rate through Inhibiting Glycolytic Metabolism.

机构信息

Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China.

Department of Emergency, Cangzhou Central Hospital, Cangzhou, China.

出版信息

Chemotherapy. 2022;67(3):132-141. doi: 10.1159/000523905. Epub 2022 Mar 4.

Abstract

INTRODUCTION

Quercetin has been reported to have antitumor activity of a wide range of cancers, including breast, lung, colon, prostate. Here, we investigated the protective role of quercetin in glioblastoma (GBM), which causes a higher risk of morbidity and mortality, and explored the antitumor effects of quercetin on GBM using the U87MG and T98G cells and GBM mouse models.

METHODS

Cell viability and colony formation assays were performed by CCK-8 and clone-formation assays. GBM xenograft mouse model was established to evaluate the tumor burden of mice treated with or without quercetin. To investigate spontaneous locomotor activity and survival rate of mice, orthotopic transplantation was performed through brain stereotaxic injection of U87 cells. Seahorse and Western blot were performed to examine the alteration of glycolytic metabolism GBM.

RESULTS

We found that quercetin administration inhibited GBM cell proliferation and promoted cell apoptosis in vitro. Quercetin suppressed GBM growth, restored spontaneous locomotor activity, and improved survival rate without toxicity to peripheral organs in vivo. Moreover, quercetin inhibited glycolytic metabolism in tumor tissue.

DISCUSSION/CONCLUSION: Mechanistically, quercetin inhibited proliferation and angiogenesis, promoted cancer cell apoptosis, and finally improved locomotor activity and survival by inhibiting the glycolytic metabolism in GBM tissues, suggesting that quercetin is a potential drug for the treatment of GBM.

摘要

简介

槲皮素已被报道具有广泛的抗肿瘤活性,包括乳腺癌、肺癌、结肠癌和前列腺癌。在这里,我们研究了槲皮素对神经胶质瘤(GBM)的保护作用,GBM 导致更高的发病率和死亡率,并使用 U87MG 和 T98G 细胞和 GBM 小鼠模型探索了槲皮素对 GBM 的抗肿瘤作用。

方法

通过 CCK-8 和克隆形成实验进行细胞活力和集落形成实验。建立 GBM 异种移植小鼠模型,以评估用或不用槲皮素治疗的小鼠的肿瘤负担。为了研究小鼠的自发运动活性和存活率,通过脑立体定向注射 U87 细胞进行原位移植。进行 Seahorse 和 Western blot 以检查 GBM 中糖酵解代谢的变化。

结果

我们发现槲皮素给药抑制了 GBM 细胞的增殖,并在体外促进了细胞凋亡。槲皮素抑制了 GBM 的生长,恢复了自发运动活性,并提高了存活率,而对周围器官没有毒性。此外,槲皮素抑制了肿瘤组织中的糖酵解代谢。

讨论/结论:从机制上讲,槲皮素通过抑制 GBM 组织中的糖酵解代谢,抑制增殖和血管生成,促进癌细胞凋亡,最终改善运动活性和存活,表明槲皮素是治疗 GBM 的潜在药物。

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