Merrick Michael, Mimlitz Michael J, Weeder Catherine, Akhter Haris, Bray Allie, Walther Andrew, Nwakama Chisom, Bamesberger Joe, Djam Honour, Abid Kaamil, Ekpenyong Andrew
Department of Physics, Creighton University, Omaha, NE, 68178, USA.
Department of Biology, Creighton University, Omaha, NE, 68178, USA.
Biochem Biophys Rep. 2021 Jul 13;27:101071. doi: 10.1016/j.bbrep.2021.101071. eCollection 2021 Sep.
Although radiotherapy and most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis strategies alongside chemotherapy and radiotherapy. An important step in the metastatic cascade is migration. It is the first step in metastasis via local invasion. Here we address the question whether ionizing radiation and/or chemotherapy might inadvertently promote metastasis and/or invasiveness by enhancing cell migration. We used a standard laboratory irradiator, Faxitron CellRad, to irradiate both non-cancer (HCN2 neurons) and cancer cells (T98G glioblastoma) with 2 Gy, 10 Gy and 20 Gy of X-rays. Paclitaxel (5 μM) was used for chemotherapy. We then measured the attachment and migration of the cells using an electric cell substrate impedance sensing device. Both the irradiated HCN2 cells and T98G cells showed significantly (p < 0.01) enhanced migration compared to non-irradiated cells, within the first 20-40 h following irradiation with 20 Gy. Our results suggest that cell migration should be a therapeutic target in anti-metastasis/anti-invasion strategies for improved radiotherapy and chemotherapy outcomes.
尽管放疗和大多数抗癌药物都针对癌细胞的增殖，但转移，即癌细胞从原发肿瘤扩散到身体其他组织和器官并在那里形成新肿瘤的复杂过程，导致了超过90%的癌症死亡。因此，除了化疗和放疗之外，迫切需要抗转移策略。转移级联反应中的一个重要步骤是迁移。它是通过局部侵袭发生转移的第一步。在这里，我们探讨电离辐射和/或化疗是否可能通过增强细胞迁移而无意中促进转移和/或侵袭性这一问题。我们使用标准实验室辐照仪Faxitron CellRad，用2 Gy、10 Gy和20 Gy的X射线照射非癌细胞（HCN2神经元）和癌细胞（T98G胶质母细胞瘤）。使用紫杉醇（5 μM）进行化疗。然后我们使用电细胞基质阻抗传感装置测量细胞的附着和迁移。与未照射的细胞相比，在用20 Gy照射后的最初20 - 40小时内，照射后的HCN2细胞和T98G细胞均显示出显著（p < 0.01）增强的迁移。我们的结果表明，细胞迁移应该成为抗转移/抗侵袭策略中的一个治疗靶点，以改善放疗和化疗的效果。
