Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells.

Abstract

Castration-resistant prostate cancer shows resistance to not only androgen deprivation therapy (ADT) but also X-ray therapy. On the other hand, carbon ion beams have a high biological effect and are used for various cancers showing resistance to X-ray therapy. The purposes of this study are to clarify the difference in the sensitivity of Castration-resistant prostate cancer to X-ray and carbon ion beams and to elucidate the mechanism. The androgen-insensitive prostate cancer cell line LNCaP-LA established by culturing the androgen-sensitive prostate cancer cell line LNCaP for 2 years in androgen-free medium was used for this study. First, colony formation assays were performed to investigate its sensitivity to X-ray and carbon ion beams. Next, DNA mutation analysis on 409 cancer-related genes and comprehensive transcriptome analysis (RNA-seq) were performed with a next-generation sequencer. Lethal dose 50 values of X-rays for LNCaP and LNCaP-LA were 1.4 Gy and 2.8 Gy, respectively (P < 0.01). The Lethal dose 50 values of carbon ion beams were 0.9 Gy and 0.7 Gy, respectively (P = 0.09). On DNA mutation analysis, AR mutation was observed specifically in LNCaP-LA. From RNA-seq, 181 genes were identified as differentially expressed genes (DEGs; FDR <0.10, P < 0.00076) between LNCaP and LNCaP-LA. Function analysis suggested that cell death was suppressed in LNCaP-LA, and pathway analysis suggested that the NRF2-pathway involved in intracellular oxidative stress prevention was activated in LNCaP-LA. LNCaP-LA showed X-ray resistance compared to LNCaP and sensitivity to carbon ion beams. The AR mutation and the NRF2-pathway were suggested as causes of resistance.

• Authors: Mototaro Iwanaga, Hidemasa Kawamura, Nobuteru Kubo, Tatsuji Mizukami, Takahiro Oike, Hiro Sato, Yoshiyuki Miyazawa, Yoshitaka Sekine, Reika Kawabata-Iwakawa, Masahiko Nishiyama, Tatsuya Ohno, Takashi Nakano
• Journal: Journal of radiation research (J Radiat Res) Vol. 63 Issue 4 Pg. 585-590 (Jul 19 2022) ISSN: 1349-9157 [Electronic] England
• PMID: 35589101 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Androgen Antagonists
• NF-E2-Related Factor 2
• Receptors, Androgen
• Carbon
• DNA

Topics

• Androgen Antagonists (therapeutic use)
• Carbon (therapeutic use)
• Castration
• Cell Line, Tumor
• DNA
• Humans
• Male
• NF-E2-Related Factor 2
• Prostatic Neoplasms (drug therapy, genetics, radiotherapy)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, genetics, radiotherapy)
• Receptors, Androgen (genetics, metabolism, therapeutic use)
• X-Rays