Dataset Information

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.

SUBMITTER: Chevalier F

PROVIDER: S-EPMC6732854 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

High LET Radiation Overcomes <i>In Vitro</i> Resistance to X-Rays of Chondrosarcoma Cell Lines.

Chevalier Francois F Hamdi Dounia Houria DH Lepleux Charlotte C Temelie Mihaela M Nicol Anaïs A Austry Jean Baptiste JB Lesueur Paul P Vares Guillaume G Savu Diana D Nakajima Tetsuo T Saintigny Yannick Y

Technology in cancer research & treatment 20190101

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 <i>in vitro</i>. 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 ...[more]

PMID: 31495269

Similar Datasets

Project description:BackgroundDespite encouraging results with the proteasome inhibitor bortezomib in the treatment of hematologic malignancies, emergence of resistance can limit its efficacy, hence calling for novel strategies to overcome bortezomib-resistance. We previously showed that bortezomib-resistant human leukemia cell lines expressed significantly lower levels of immunoproteasome at the expense of constitutive proteasomes, which harbored point mutations in exon 2 of the PSMB5 gene encoding the ?5 subunit. Here we investigated whether up-regulation of immunoproteasomes by exposure to interferon-? restores sensitivity to bortezomib in myeloma and leukemia cell lines with acquired resistance to bortezomib.MethodsRPMI-8226 myeloma, THP1 monocytic/macrophage and CCRF-CEM (T) parental cells and sub lines with acquired resistance to bortezomib were exposed to Interferon-? for 24-48 h where after the effects on proteasome subunit expression and activity were measured, next to sensitivity measurements to proteasome inhibitors bortezomib, carfilzomib, and the immunoproteasome selective inhibitor ONX 0914. At last, siRNA knockdown experiments of ?5i and ?1i were performed to identify the contribution of these subunits to sensitivity to proteasome inhibition. Statistical significance of the differences were determined using the Mann-Whitney U test.ResultsInterferon-? exposure markedly increased immunoproteasome subunit mRNA to a significantly higher level in bortezomib-resistant cells (up to 30-fold, 10-fold, and 6-fold, in ?1i, ?5i, and ?2i, respectively) than in parental cells. These increases were paralleled by elevated immunoproteasome protein levels and catalytic activity, as well as HLA class-I. Moreover, interferon-? exposure reinforced sensitization of bortezomib-resistant tumor cells to bortezomib and carfilzomib, but most prominently to ONX 0914, as confirmed by cell growth inhibition studies, proteasome inhibitor-induced apoptosis, activation of PARP cleavage and accumulation of polyubiquitinated proteins. This sensitization was abrogated by siRNA silencing of ?5i but not by ?1i silencing, prior to pulse exposure to interferon-?.ConclusionDownregulation of ?5i subunit expression is a major determinant in acquisition of bortezomib-resistance and enhancement of its proteasomal assembly after induction by interferon-? facilitates restoration of sensitivity in bortezomib-resistant leukemia cells towards bortezomib and next generation (immuno) proteasome inhibitors.

Dataset Information

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

Publications

High LET Radiation Overcomes <i>In Vitro</i> Resistance to X-Rays of Chondrosarcoma Cell Lines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets