RRC ID |
64633
|
著者 |
Maeda K, Yasui H, Yamamori T, Matsuura T, Takao S, Suzuki M, Matsuda A, Inanami O, Shirato H.
|
タイトル |
A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-β-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam.
|
ジャーナル |
PLoS One
|
Abstract |
The effect of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair. This study demonstrated that ECyd enhances proton-induced cell killing at all positions of SOBP, except for the distal region and minimizes the site-dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer for proton therapy that may be useful because it levels the biological dose within SOBP, which improves tumor control and reduces the risk of adverse effects at the distal edge of SOBP.
|
巻・号 |
11(11)
|
ページ |
e0166848
|
公開日 |
2016-1-1
|
DOI |
10.1371/journal.pone.0166848
|
PII |
PONE-D-16-19203
|
PMID |
27875573
|
PMC |
PMC5119790
|
MeSH |
A549 Cells
Animals
Antineoplastic Agents / pharmacology*
Cell Death
Cricetinae
Cricetulus
Cytosine* / analogs & derivatives
Cytosine* / pharmacology
DNA Breaks, Double-Stranded / drug effects
DNA Breaks, Double-Stranded / radiation effects
DNA Repair / drug effects
DNA Repair / radiation effects
Dose-Response Relationship, Drug
Humans
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Lung Neoplasms / therapy*
Proton Therapy*
Radiation-Sensitizing Agents / pharmacology*
Tumor Suppressor Protein p53 / metabolism
|
IF |
2.74
|
リソース情報 |
ヒト・動物細胞 |
V79(RCB0008)
A549(RCB0098) |