Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma.
Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma.
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胶质母细胞瘤中EGFR降低和miR-221升高与替莫唑胺和放疗耐药增加相关。
DOI：
10.1038/s41598-020-74746-x
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发表时间：
2020-10-20
影响因子：
4.6
通讯作者：
Luwor RB
中科院分区：
文献类型：
--
作者：
Areeb Z;Stuart SF;West AJ;Gomez J;Nguyen HPT;Paradiso L;Zulkifli A;Jones J;Kaye AH;Morokoff AP;Luwor RB
尽管使用替莫唑胺和放疗进行积极治疗，并对替代疗法进行了广泛研究，但胶质母细胞瘤患者的生存率几乎没有改善。中位生存时间保持在12至15个月之间，主要是由于治疗抵抗和肿瘤复发。在这项研究中，我们的目的是探索治疗耐药背后的潜在机制，以及临床上抗EGFR治疗缺乏成功。在产生许多治疗抗性胶质母细胞瘤细胞系后，我们观察到抗性细胞系缺乏EGFR活化和表达。此外，细胞活力测定显示，与亲本细胞系相比，耐药细胞对抗EGFR药物的敏感性显著降低。为了进一步验证我们细胞中的耐药机制，microRNA预测软件将miR-221鉴定为EGFR表达的负调节因子。miR-221在我们的耐药细胞系中上调，这种上调导致我们培养的细胞系和一大群胶质母细胞瘤患者肿瘤组织中EGFR表达显著降低。
Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.
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DOI：
10.1007/978-1-4614-3146-6_3
发表时间：
2012-01-01
期刊：
GLIOMA: IMMUNOTHERAPEUTIC APPROACHES
影响因子：
--
作者：
Johnson, Derek R.;Chang, Susan M.
通讯作者：
Chang, Susan M.
影响因子：
2
作者：
Cher, Lawrence;Rosenthal, Mark A.;Giles, Graham G.
通讯作者：
Giles, Graham G.
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R
影响因子：
3.4
作者：
Areeb, Zammam;Stylli, Stanley S.;Luwor, Rodney B.
通讯作者：
Luwor, Rodney B.
影响因子：
3.9
作者：
Kreisl, Teri N.;Lassman, Andrew B.;Abrey, Lauren E.
通讯作者：
Abrey, Lauren E.