High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines

Abstract

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness = 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness = 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.

Radiosensitizing Effect of Celastrol by Inhibiting G2/M Phase Arrest Induced by the c-myc Gene of Human SW1353 Chondrosarcoma Cells: Network and Experimental Analyses

“…Chondrosarcoma was strongly resistant to X-rays, which has caused great limitations in the treatment of chondrosarcoma [ 7 ]. Accumulating evidence indicates that cell cycle G2/M phase arrest is one of the key factors to enhance the sensitivity of radiotherapy [ 15 , 28 , 29 ].…”

“…We also found that the expression of P21 protein in chondrosarcoma cells decreased with the increase of drug concentration, which may be related to the multitarget effect of celastrol and the time of action of drugs or radiation. Further research is needed [ 5 , 7 , 42 ]. In vitro experiments confirmed that celastrol can interfere with cyclin-dependent protein kinases by inhibiting the MYC gene-encoding transcription factors and lead to radiosensitization, which verified the accuracy of the conclusions of network pharmacology.…”

“…However, for certain parts of the body, such as the pelvis or skull, it is difficult to achieve broad-side resection and the incidence of recurrence and metastasis is still high [ 6 ]. Radiotherapy is still a better palliative treatment [ 7 , 8 ].…”

A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

“…X-rays irradiations were performed, as previously described [ 12 , 30 ], at room temperature (20 °C) with a tube tension of 225 kV, a copper filter, and an intensity of 1 mA corresponding to a dose rate of 0.2 Gy/min on the Pxi XradSmart 225cX irradiator, dedicated to preclinical research. The dose rate was measured inside flasks with thermoluminescent dosimeters in the irradiation conditions.…”

Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions

“…X-ray irradiations were performed with a PxiXradSmart 225cX irradiator using a tube tension of 225 kV, as previously described [21][22][23][24][25][26][27][28][29][30], and C-ion irradiations were performed in the GANIL facility (Caen, France) using the high-energy beam line IRABAT, as previously described [31,32]. For C-ions, a LET of 73 keV/µm was selected to reproduce clinical conditions.…”