癌症干细胞对低强度超声的生物力学反应。

Biomechanical Response of Cancer Stem Cells to Low-Intensity Ultrasound.

机构信息

The First Affiliated Hospital of University of South China, Medical Imaging Centre, Hengyang Medical School, University of South China, 69 Chuanshan Road, Hengyang 421001, China; Institute of Medical Imaging, University of South China, Hengyang 421001, Hunan, China; Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510000, Guangdong, China.

出版信息

J Biomech Eng. 2023 Sep 1;145(9). doi: 10.1115/1.4062299.

DOI:10.1115/1.4062299

PMID:37043237

Abstract

The presence of stem cells in cancer may increase the chances of drug resistance and invasiveness. Low-intensity ultrasound (LIUS) can regulate the biological and mechanical properties of cells and participate in cellular migration and differentiation. Although LIUS has shown significant potential in cancer treatment, the effects of LIUS on migration and drug resistance of cancer stem cells (CSCs) are unclear from a biomechanical perspective. Hence, the objective of this work is to analyze the biomechanical response of LIUS to CSCs. In this study, we selected human ovarian cancer cell line A2780 and ovarian cancer stem cells (OCSCs) were enriched from A2780 cells and observed that OCSCs had higher drug sensitivity and lower invasiveness than A2780 cells after LIUS exposure. Furthermore, we further analyzed the changes in cell morphology, cytoskeleton, and membrane stiffness of A2780 cells and OCSCs at various intensities of LIUS, these results showed that LIUS could induce morphological changes, F-actin formation and increase membrane stiffness, which could help to suppress migration and reduce the drug resistance of OCSCs. Our findings will help establish a better understanding of the biomechanical response to LIUS in CSCs, and future studies on cancer will benefit from the careful consideration of the cellular response of CSCs to LIUS stimulation, ultimately allowing for the development of more effective therapies.

摘要

肿瘤干细胞的存在可能会增加药物耐药性和侵袭性。低强度超声（LIUS）可以调节细胞的生物和机械特性，并参与细胞迁移和分化。尽管 LIUS 在癌症治疗中显示出了巨大的潜力，但从生物力学的角度来看，LIUS 对癌症干细胞（CSCs）迁移和耐药性的影响尚不清楚。因此，本工作的目的是分析 LIUS 对 CSCs 的生物力学响应。在这项研究中，我们选择了人卵巢癌细胞系 A2780，并从 A2780 细胞中富集了卵巢癌症干细胞（OCSCs），结果发现，与 A2780 细胞相比，OCSCs 经 LIUS 暴露后具有更高的药物敏感性和更低的侵袭性。此外，我们进一步分析了不同强度 LIUS 作用下 A2780 细胞和 OCSCs 的细胞形态、细胞骨架和细胞膜硬度的变化，结果表明，LIUS 可以诱导形态变化、F-肌动蛋白形成和增加细胞膜硬度，从而有助于抑制 OCSCs 的迁移并降低其耐药性。我们的研究结果将有助于更好地理解 CSCs 对 LIUS 的生物力学响应，并为未来的癌症研究提供帮助，使人们在考虑 CSCs 对 LIUS 刺激的细胞反应时更加谨慎，最终开发出更有效的治疗方法。