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

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.