Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe

被引：37

作者：

Amornwichet, Napapat ^{[1
,2
]}

Oike, Takahiro ^{[1
,3
]}

Shibata, Atsushi ^{[4
]}

Ogiwara, Hideaki ^{[3
]}

Tsuchiya, Naoto ^{[3
]}

Yamauchi, Motohiro ^{[5
]}

Saitoh, Yuka ^{[1
]}

Sekine, Ryota ^{[4
]}

Isono, Mayu ^{[6
]}

Yoshida, Yukari ^{[6
]}

Ohno, Tatsuya ^{[6
]}

Kohno, Takashi ^{[3
]}

Nakano, Takashi ^{[1
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Radiat Oncol, Maebashi, Gunma, Japan

[2] Chulalongkorn Univ, Dept Radiol, Bangkok, Thailand

[3] Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 104, Japan

[4] Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gunma, Japan

[5] Nagasaki Univ, Atom Bomb Dis Inst, Div Radiat Biol & Protect, Nagasaki 852, Japan

[6] Gunma Univ, Heavy Ion Med Ctr, Maebashi, Gunma, Japan

来源：

PLOS ONE | 2014年 / 9卷 / 12期

基金：

日本学术振兴会;

关键词：

RADIATION-THERAPY; DNA-DAMAGE; P53; STATUS; REPLICATION STRESS; GLIOBLASTOMA CELLS; CYCLE CHECKPOINTS; IN-VITRO; CARCINOMA; OPTIMIZATION; SENSITIVITY;

D O I：

10.1371/journal.pone.0115121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background and Purpose: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies. Materials and Methods: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53(+/+) and p53(-/-), respectively) were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA double-strand breaks (DSBs) by immunostaining of phosphorylated H2AX (gamma H2AX), and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3. Results: The p53(-/-) cells were more resistant than the p53(+/+) cells to X-ray irradiation, while the sensitivities of the p53(+/+) and p53(-/-) cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53(+/+) cells but not the p53(-/-) cells. In the p53(-/-) cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring long-retained DSBs at 24 h post-irradiation. Conclusions: Efficient induction of mitotic catastrophe in apoptosis-resistant p53-deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.

引用

页数：16

共 37 条

[1] G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer [J].