Heterogeneity of chondrosarcomas response to irradiations with X-rays and carbon ions: A comparative study on five cell lines

Girard, Nicolas; Lhuissier, Eva; Aury-Landas, Juliette; Cauvard, Olivier; Lenté, Marion; Boittin, Martine; Baugé, Catherine; Boumédiene, Karim

doi:10.1016/j.jbo.2020.100283

Cited by 11 publications

(9 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Chondrosarcoma is a highly malignant tumor characterized by the production of the cartilage matrix by tumor cells, which is the second most commonly malignant bone tumor, with an incidence of 1 in 1,000,000 people [ 1 , 2 ]. Chondrosarcoma itself has poor blood supply and lymphatic circulation and is insensitive to radiotherapy and chemotherapy; local or extensive surgical resection is the main method of treatment of chondrosarcoma to prevent local recurrence and distant metastasis [ 3 – 5 ]. 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 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

[Retracted] 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

Jin

Zhang

Han

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Objective. Studies have unveiled that the components of Tripterygium wilfordii Hook F (TWHF) such as celastrol could attenuate apoptosis and proliferation of various tumor cells. This study is focused on the radiosensitization effect and apoptotic pathways of celastrol via the inhibition of the c-myc gene and the influence of which combined with radiotherapy on the proliferation, apoptosis, invasion, and metastasis of chondrosarcoma cells. Methods. A variety of bioinformatic tools were applied to explore the expression level and prognosis of the c-myc gene in different tumor cells and chondrosarcoma cells. We used pharmacology network to analyze the components, pathways, targets, molecular functions of TWHF and explore the relevant effective components over the MYC gene. Clone formation assay, CCK-8 assay, flow cytometry, and transwell migration assay were applied to detect the effects of celastrol on the expression of c-myc gene, cell apoptosis, and cell cycle. Radiation therapy was used to observe the radiosensitization effect of celastrol on chondrosarcoma. Results. This study shows that the c-myc gene is overexpressed in various tumor cells and bone tumor cells to varying degrees. Celastrol can significantly inhibit the expression of the c-myc gene, induce G2/M phase arrest through regulation of G2/M phase-related proteins, and promote SW1353 cell apoptosis through the mitochondrial signaling pathway. In addition, we also found that the use of triptorubin to inhibit c-myc gene expression in combination with radiotherapy can increase the osteosarcoma cells’ apoptosis rate through the mitochondrial signaling pathway significantly. Conclusions. Our study validated the radiosensitization effect of celastrol through knocking down the expression of the c-myc gene to induce G2/M phase arrest and provides a new idea for the treatment of refractory or recurrent chondrosarcoma that is not sensitive to radiotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

[Retracted] 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

Jin

Zhang

Han

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Despite the utmost importance for clinical-therapeutic applications, only a few publications on the cellular processes are known. Girard et al demonstrated that chondrosarcoma cells respond differently to IR due to their strong genetic heterogeneity [ 17 ]. In our previous study, we were able to show that both X-ray and proton IR resulted in reduced chondrosarcoma cell survival and a decreased ability to form colonies [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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

Lohberger

Barna

Glänzer

et al. 2022

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…In patients with chondrosarcoma with unfavorable initial characteristics, a high grade and incomplete resection, postoperative radiotherapy is an expedient option; it reduces the risk of local recurrence and improves 5-year disease-free survival from 64.2 to 71.8% ( 22 ). Chondrosarcomas exhibit variable response to irradiation, possibly due to their strong genetic heterogeneity, which is also evident in different chondrosarcoma cell lines ( 23 , 24 ). In this context, it is particularly important to gain new insights into the underlying tumor biology of chondrosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

et al. 2021

View full text Add to dashboard Cite

Chondrosarcomas represent a heterogeneous group of primary bone cancers that are characterized by hyaline cartilaginous neoplastic tissue and are predominantly resistant to radiation and chemotherapy. However, adjuvant radiotherapy is often recommended in inoperable cases or after incomplete resections. To improve the efficiency of treatment, the present study tested a combination therapy with ionizing radiation (IR) and the proteasome inhibitor bortezomib. Using a three-dimensional (3D) spheroid model, 0-20 Gy of IR was applied to chondrosarcoma cells and healthy human chondrocytes. Following combined treatment with IR and bortezomib, the cell cycle distribution, apoptotic induction, the survivin pathway, autophagy and DNA damage were evaluated. Both cell types exhibited a slight decrease in viability following increasing doses of IR; the chondrosarcoma cells demonstrated a significant dose-dependent increase in the expression levels of the DNA damage marker histone H2AX phosphorylation at serine 139 (γH2AX). The combination treatment with bortezomib significantly decreased the cell viability after 48 h compared with that in irradiated cells. High-dose IR induced a G 2 /M phase arrest, which was accompanied by a decrease in the number of cells at the G 1 and S phase. Co-treatment with bortezomib changed the distribution of the cell cycle phases. The mRNA expression levels of the proapoptotic genes Bcl-2-associated X protein (Bax) and Bak were significantly increased by bortezomib treatment and combination therapy with IR. In addition, the combination therapy resulted in a synergistic decrease of the expression levels of survivin and its corresponding downstream pathway molecules, including heat shock protein 90, X-linked inhibitor of apoptosis protein, smad 2 and smad 3. Comparative analyses of γH2AX at 1 and 24 h post-IR revealed efficient DNA repair in human chondrosarcoma cells. Therefore, additional bortezomib treatment may only temporarily improve the radiation sensitivity of chondrosarcoma cells. However, the inhibition of the survivin pathway by the combined treatment with IR and bortezomib, observed in the present study, revealed a novel aspect in the tumor biology of chondrosarcoma 3D spheroid cultures and may represent a potential target for therapy.

show abstract

Heterogeneity of chondrosarcomas response to irradiations with X-rays and carbon ions: A comparative study on five cell lines

Cited by 11 publications

References 46 publications

[Retracted] 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

[Retracted] 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

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

Effects of a combined therapy of bortezomib and ionizing radiation on chondrosarcoma three-dimensional spheroid cultures

Contact Info

Product

Resources

About