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葡萄糖影响细胞对替莫唑胺和地塞米松的反应。

Glucose Influences the Response of Cells to Temozolomide and Dexamethasone.

机构信息

Department of Pharmacology, School of Medicine in Katowice, 49613Medical University of Silesia, Katowice, Poland.

Student Research Circle at the Department of Pharmacology, School of Medicine in Katowice, 49613Medical University of Silesia, Katowice, Poland.

出版信息

Cancer Control. 2022 Jan-Dec;29:10732748221075468. doi: 10.1177/10732748221075468.

Abstract

OBJECTIVE

Current research indicates that weakness of glucose metabolism plays an important role in silencing of invasiveness and growth of hypoxic tumors such as GBM. Moreover, there are indications that DXM, frequently used in treatment, may support GBM energy metabolism and provoke its recurrence.

METHODS

We carried out in vitro experiments on the commercial T98G cell line and two primary GBM lines (HROG02, HROG17) treated with TMZ and/or DXM in physiological oxygen conditions for GBM (2.5% oxygen) and for comparison, in standard laboratory conditions (20% oxygen). The influence of different glucose levels on selected malignancy features of GBM cells-cellular viability and division, dynamic of cell culture changes, colony formation and concentration of InsR have been elevated.

RESULTS

Under 2.5% oxygen and high glucose concentration, an attenuated cytotoxic effect of TMZ and intensification of malignancy features in all glioblastoma cell lines exposed to DXM was seen. Furthermore, preliminary retrospective analysis to assess the correlation between serum glucose levels and Ki-67 expression in surgical specimens derived from patients with GBM (IV) treated with radio-chemotherapy and prophylactic DXM therapy was performed.

CONCLUSION

The data suggest a link between the in vitro study results and clinical data. High glucose can influence on GBM progression through the promotion of the following parameters: cell viability, dispersal, InsR expression and cell proliferation (Ki-67). However, this problem needs more studies and explain the mechanism of action studied drugs.

摘要

目的

目前的研究表明,葡萄糖代谢的减弱在沉默缺氧肿瘤(如 GBM)的侵袭性和生长中起着重要作用。此外,有迹象表明,经常用于治疗的 DXM 可能支持 GBM 能量代谢并引发其复发。

方法

我们在体外实验中使用 TMZ 和/或 DXM 处理商业 T98G 细胞系和两种原发性 GBM 系(HROG02、HROG17),分别在生理氧条件下(GBM 为 2.5%氧)和标准实验室条件下(20%氧)进行处理。研究了不同葡萄糖水平对 GBM 细胞选择的恶性特征的影响,包括细胞活力和分裂、细胞培养变化的动态、集落形成和 InsR 浓度。

结果

在 2.5%氧和高葡萄糖浓度下,我们观察到 DXM 暴露下所有 GBM 细胞系的 TMZ 细胞毒性作用减弱和恶性特征增强。此外,我们还进行了初步回顾性分析,以评估接受放化疗和预防性 DXM 治疗的 GBM(IV 期)患者手术标本中血清葡萄糖水平与 Ki-67 表达之间的相关性。

结论

数据表明体外研究结果与临床数据之间存在联系。高葡萄糖可以通过促进以下参数来影响 GBM 的进展:细胞活力、分散、InsR 表达和细胞增殖(Ki-67)。然而,这个问题需要更多的研究来解释研究药物的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be0b/8891890/15bda50d5e83/10.1177_10732748221075468-fig1.jpg

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