The Effect Of X-ray On The Mechanical Properties Of Cancer Cellsand Its Mechanism

Up to now,tumor is still one of the major diseases that cause human death and endanger human health.Radiation therapy is one of the main methods of cancer treatment at present.DNA is the main target molecule for ionizing radiation to act on biological targets.Ionizing radiation-induced DNA damage is central to the study of biological mechanisms of radiation and a key mechanism for the efficacy of cancer therapy.Therefore,the DNA damage response process of ionizing radiation has always been the focus of research by scholars at home and abroad.Recent studies have found that cell mechanical properties affect many important cellular functions and physiological processes,such as cell motility,invasion and metastasis,and genome integrity.However,how the radiation-induced DNA damage response affects cellular mechanical properties and how cellular mechanical properties affect DNA damage remains unclear.An important reason is the lack of suitable tools for measuring the mechanical properties of cells.In addition,ionizing radiation enhances cell adhesion and causes cell flattening,which affects the accuracy of measuring cell mechanical properties in the adherent state.To this end,this paper independently designed and established a cell mechanics measurement device based on ultrasonic standing wave technology,which can quickly and non-destructively measure the compressibility of cancer cells in a suspended state.Compressibility is an important parameter of the mechanical properties of cells and is a reflection of the overall modulus of the cell.Combined with biological methods such as immunofluorescence and cell viability experiments,this paper systematically studies the effects of X-rays on the mechanical properties of cancer cells.The main work and conclusions are as follows:1.Establish an ultrasonic standing wave microfluidic chip device.The device enables non-contact manipulation of cells in fluids to measure cell compressibility.In the process of measuring cell compressibility,the damage to cells is small,and the measurement speed is fast and the throughput is high.2.Measure the compressibility of various cancer cell lines based on an ultrasonic standing wave microfluidic device.The aggressive breast cancer cell line MDA-MB231 is more compressible(ie,softer)than the non-invasive MCF-7,enabling measurement of the compressibility of cancer cells with different invasive abilities.Breast cancer cell line MDA-MB231,lung adenocarcinoma cell line A549 and colon cancer cell line HCT116 have differences in compressibility and size.3.X-rays affect the mechanical properties of cells.After 3 hours of X-ray irradiation,the compressibility of cells increased significantly,and the change of compressibility was related to radiation dose and cell type.4.The effect and mechanism of radiation-induced DNA damage response on cellular mechanical properties.Inhibition of DNA damage response processes suppressed radiation-induced changes in compressibility.Heterochromatin structure and cytoskeletal proteins were further studied.The fluorescence intensity of heterochromatin decreased 3 h after irradiation,and the chromatin structure in the nucleus decondensed,but the fluorescence intensity and tissue distribution of cytoskeletal proteins did not change significantly.This revealed that radiation-induced changes in compressibility were associated with decondensation of chromatin in the nucleus in response to DNA damage.5.Changes in cellular mechanical properties affect the response to radiation-induced DNA damage.By adding the myosin-inhibiting drug blebbistatin before X-ray irradiation,the stress on the nucleus was reduced,the cell compressibility was increased,and the radiation-induced 53BP1 foci and yH2AX foci were significantly reduced,revealing that the increase in cell compressibility would Attenuates radiation-induced DNA damage.Through the research in this paper,the compressibility measurement of cancer cells with different types and different invasive abilities is achieved.Moreover,the inter-regulation mechanism between X-ray-induced DNA damage response and the mechanical properties of cancer cells was revealed,providing new ideas for in-depth understanding of ionizing radiation-induced biological effects.