Lee Won Seok, Seo Seung-Jun, Chung Hye Kyung, Park Jang Woo, Kim Jong-Ki, Kim Eun Ho
Department of Biochemistry, School of Medicine, Daegu Catholic University 33 17-gil, Duryugongwon-ro, Nam-gu, Daegu, Republic of Korea.
Department of Biomedical Engineering and School of Medicine, Daegu Catholic University Nam-gu, Daegu 42472, Republic of Korea.
Am J Cancer Res. 2021 Sep 15;11(9):4582-4594. eCollection 2021.
Few advances in GBM treatment have been made since the initiation of the Stupp trials in 2005. Experimental studies on immunotherapy drugs, molecular inhibitors, radiation dosage escalation and vascular growth factor blockers have all failed to provide satisfactory outcomes. TTFields therapy, on the other hand, have emerged as a viable substitute to therapies like radiation in GBM patients having a highly immunosuppressive tumor microenvironment. To enhance the biofunctional impacts, we explored the combination events with TTFields and proton treatment in this study. We conducted a cell viability test, a cell death detection evaluation, a ROS analysis, a three-dimensional (3D) culture system, and a migration assay. The combination of proton radiation and TTFields therapy laid a substantial anticancer impact on the F98 and U373 as compared to the consequences of either of these therapies used separately. The combination proton beam therapy used by TTFields was very successful in curbing GBM from migrating. GBM cell metastasis is restricted by TTFields combined proton by downregulating the MAPK, NF-κB, and PI3K/AKT indicating pathways, caused by reduced EMT marker expression. These findings furnish biological proof for the molecular grounds of TTFields in combination with proton used for GBM therapy.
自2005年开展Stupp试验以来,胶质母细胞瘤(GBM)治疗方面几乎没有取得进展。对免疫治疗药物、分子抑制剂、放射剂量递增和血管生长因子阻滞剂的实验研究均未能取得令人满意的结果。另一方面,肿瘤治疗电场(TTFields)疗法已成为在具有高度免疫抑制肿瘤微环境的GBM患者中替代放疗等疗法的可行选择。为了增强生物功能影响,我们在本研究中探索了TTFields与质子治疗的联合应用。我们进行了细胞活力测试、细胞死亡检测评估、活性氧(ROS)分析、三维(3D)培养系统和迁移试验。与单独使用这两种疗法的结果相比,质子放疗与TTFields疗法的联合对F98和U373细胞产生了显著的抗癌作用。TTFields联合使用的质子束疗法在抑制GBM迁移方面非常成功。TTFields联合质子可通过下调MAPK、NF-κB和PI3K/AKT信号通路,减少上皮-间质转化(EMT)标志物表达,从而限制GBM细胞转移。这些发现为TTFields联合质子用于GBM治疗的分子机制提供了生物学证据。