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基质硬度会影响宫颈鳞癌细胞的形态、增殖和放射敏感性。

Substrate stiffness affects the morphology, proliferation, and radiosensitivity of cervical squamous carcinoma cells.

机构信息

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, China.

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, China.

出版信息

Tissue Cell. 2022 Feb;74:101681. doi: 10.1016/j.tice.2021.101681. Epub 2021 Nov 24.

Abstract

Cervical cancer is associated with the highest morbidity rate among gynecological cancers. Radiotherapy plays an important role in the treatment of cervical cancer. However, a considerable number of patients are radiation resistant, leading to a poor prognosis. Matrix stiffness is related to the occurrence, development, and chemoresistance of solid tumors. The association between matrix stiffness and radiosensitivity in cervical cancer cells remains unknown. Here, we sought to determine the effect of matrix stiffness on the phenotype and radiosensitivity of cervical cancer cells. Cervical squamous carcinoma SiHa cells were grown on substrates of different stiffnesses (0.5, 5, and 25 kPa). Cell morphology, proliferation, and radiosensitivity were examined. Cells grown on hard substrates displayed stronger proliferative activity, larger size, and higher differentiation degree, which was reflected in a more mature skeleton assembly, more abundant pseudopodia formation, and smaller nuclear/cytoplasmic ratio. In addition, SiHa cells exhibited stiffness-dependent resistance to radiation, possibly via altered apoptosis-related protein expression. Our findings demonstrate that matrix stiffness affects the morphology, proliferation, and radiosensitivity of SiHa cells. Tissue stiffness may be an indicator of the sensitivity of a patient to radiotherapy. Thus, the data provide insights into the diagnosis of cervical cancer and the design of future radiotherapies.

摘要

宫颈癌是妇科癌症中发病率最高的疾病。放射治疗在宫颈癌的治疗中起着重要的作用。然而,相当数量的患者对放射治疗有抗性,导致预后不良。基质硬度与实体瘤的发生、发展和化疗耐药性有关。基质硬度与宫颈癌细胞放射敏感性之间的关系尚不清楚。在这里,我们试图确定基质硬度对宫颈癌细胞表型和放射敏感性的影响。宫颈鳞癌细胞 SiHa 在不同硬度(0.5、5 和 25 kPa)的基底上生长。检测细胞形态、增殖和放射敏感性。在硬基底上生长的细胞表现出更强的增殖活性、更大的体积和更高的分化程度,这反映在更成熟的骨架组装、更多的伪足形成和更小的核/质比。此外,SiHa 细胞表现出对辐射的硬度依赖性耐药性,可能通过改变与凋亡相关的蛋白表达。我们的研究结果表明,基质硬度影响 SiHa 细胞的形态、增殖和放射敏感性。组织硬度可能是患者对放射治疗敏感性的指标。因此,这些数据为宫颈癌的诊断和未来放射治疗的设计提供了新的思路。

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