Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data

Abstract

Chondrosarcomas are particularly difficult to treat due to their resistance to chemotherapy and radiotherapy. However, particle therapy can enhance local control and patient survival rates. To improve our understanding of the basic cellular radiation response, as a function of dose and linear energy transfer (LET), we developed a novel water phantom-based setup for cell culture experiments and characterized it dosimetrically. In a direct comparison, human chondrosarcoma cell lines were analyzed with regard to their viability, cell proliferation, cell cycle, and DNA repair behavior after irradiation with X-ray, proton, and carbon ions. Our results clearly showed that cell viability and proliferation were inhibited according to the increasing ionization density, i.e., LET, of the irradiation modes. Furthermore, a prominent G2/M arrest was shown. Gene expression profiling proved the upregulation of the senescence genes CDKN1A (p21), CDKN2A (p16NK4a), BMI1, and FOXO4 after particle irradiation. Both proton or C-ion irradiation caused a positive regulation of the repair genes ATM, NBN, ATXR, and XPC, and a highly significant increase in XRCC1/2/3, ERCC1, XPC, and PCNA expression, with C-ions appearing to activate DNA repair mechanisms more effectively. The link between the physical data and the cellular responses is an important contribution to the improvement of the treatment system.

Biomimetic Nanoplatform for Dual‐Targeted Clearance of Activated and Senescent Cancer‐Associated Fibroblasts to Improve Radiation Resistance in Breast Cancer

“…CDKN2A (p16) and CDKN1A (p21), were significantly increased in CAFs after IR (Figure 2B). [39,40] The mRNA expression levels of TGF-𝛽, IL-6, and IL-10 were also determined. Compared with CAFs, SC CAFs showed markedly increased expression of SASPs (Figure 3C).…”

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

“…In the particular case of chondrosarcoma, in vitro studies showed a higher efficiency of carbon ions on multiple chondrosarcoma cell lines [ 10 , 82 , 101 , 102 ]. The cellular effect was directly connected with the LET of carbon ions, inducing a prolonged block of irradiated cells in the G2 phase of the cell cycle and longer-lasting unrepaired cell damage [ 101 , 103 ]. Carbon ion radiations generated a positive regulation of several DNA repair genes (ATM, NBN, ATXR, XPC, XRCC1/2/3, ERCC1, XPC, and PCNA), activating a large range of DNA repair mechanisms [ 103 ].…”