The Effect of Β-Arrestin2 Overexpression Regarding Viability and Temozolomide Treatment in High-Grade Glioma Cells.

Current Health Sciences Journal Pub Date : 2022-10-01 Epub Date: 2022-12-31 DOI:10.12865/CHSJ.48.04.07
Alexandru Oprita, Georgiana Adeline Staicu, Carina Baloi, Anica Dricu, Stefan Alexandru Artene
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Abstract

The β-arrestins (β-arr) family are proteins that regulate the signaling and trafficking of various G protein-coupled receptors. Out of the four members, β-arr 1 and 2 have been proven as essential actors behind different processes that lead to the progression of cancer as cell proliferation, migration, invasion and metastasis. In addition to this, these proteins are also capable of transmitting anti-apoptotic signals, influence tumor growth rate and drug resistance. Several studies have demonstrated that β-arr 2 overexpression corelates with an impaired overall survival and also showed that it may mediate multidrug resistance in certain types of cancer. In the current study we analyzed the effect of β-arr 2 overexpression on proliferation and how it affects Temozolomide (TMZ) response on the CL2:6 High Grade Glioma (HGG) cell line. We observed contradictory results after transfection, with β-arr 2 overexpressing cells having a superior proliferation rate after 24 and 48h, when compared to untransfected cells, while the opposite was noted after 72h. In terms of response to TMZ, we observed a similar contradictory pattern with modest differences between doses being observed at 24h, while the smallest and largest doses in our experiment produced opposite effects after 48h and 72h. This further underscores the scarcity of information regarding the exact roles and the importance of β-arrs in the intrinsic mechanisms which govern cancer cells.

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β-Arrestin2过表达对高级别胶质瘤细胞生存能力和替莫唑胺治疗的影响。
βarrestins(β-arr)家族是调节各种G蛋白偶联受体的信号传导和运输的蛋白质。在这四个成员中,β-arr1和2已被证明是导致癌症进展的不同过程(如细胞增殖、迁移、侵袭和转移)背后的重要因素。除此之外,这些蛋白质还能够传递抗凋亡信号,影响肿瘤生长速率和耐药性。几项研究表明,β-arr2过表达与总生存率受损有关,也表明它可能介导某些类型癌症的多药耐药性。在目前的研究中,我们分析了β-arr 2过表达对增殖的影响,以及它如何影响替莫唑胺(TMZ)对CL2:6高级别胶质瘤(HGG)细胞系的反应。转染后,我们观察到了相互矛盾的结果,与未转染的细胞相比,β-arr 2过表达的细胞在24和48小时后具有更高的增殖率,而在72小时后则相反。就TMZ的反应而言,我们观察到类似的矛盾模式,在24小时观察到的剂量之间存在适度差异,而我们实验中最小和最大剂量在48小时和72小时后产生相反的效果。这进一步强调了关于β-ars在控制癌症细胞的内在机制中的确切作用和重要性的信息的稀缺性。
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