Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460.
Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460.
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DOI：
10.1093/jrr/rru085
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发表时间：
2015-03
影响因子：
2
通讯作者：
Nakano T
中科院分区：
文献类型：
--
作者：
Kubo N;Noda SE;Takahashi A;Yoshida Y;Oike T;Murata K;Musha A;Suzuki Y;Ohno T;Takahashi T;Nakano T
本研究调查了卡铂和紫杉醇使人类非小细胞肺癌 (NSCLC) 细胞对碳离子束照射敏感的能力。用卡铂或紫杉醇处理的NSCLC H460细胞用X射线或碳离子束照射，并通过克隆形成存活测定评估放射敏感性。通过使用台盼蓝计数活细胞的数量来确定细胞增殖。分别通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 染色和衰老相关 β-半乳糖苷酶 (SA-β-gal) 染色评估细胞凋亡和衰老。通过蛋白质印迹分析裂解的 caspase-3、Bax、p53 和 p21 的表达。克隆存活试验证明卡铂和紫杉醇与碳离子束具有协同放射增敏作用；存活分数 (D10) 为 10% 的剂量下的增敏剂增强比 (SER) 分别为 1.21 和 1.22。同样，卡铂和紫杉醇对 X 射线显示出放射增敏作用； SER 分别为 1.41 和 1.29。细胞增殖测定验证了卡铂和紫杉醇在碳离子束和 X 射线照射下的放射增敏作用。卡铂和紫杉醇联合碳离子束治疗可增加TUNEL阳性细胞以及cleaved caspase-3和Bax的表达，表明细胞凋亡增强。联合治疗还增加了 SA-β-gal 阳性细胞以及 p53 和 p21 的表达，表明衰老增强。总之，卡铂和紫杉醇通过增强辐射诱导的细胞凋亡和衰老，使 H460 细胞对碳离子束辐射敏感。
The present study investigated the ability of carboplatin and paclitaxel to sensitize human non-small-cell lung cancer (NSCLC) cells to carbon-ion beam irradiation. NSCLC H460 cells treated with carboplatin or paclitaxel were irradiated with X-rays or carbon-ion beams, and radiosensitivity was evaluated by clonogenic survival assay. Cell proliferation was determined by counting the number of viable cells using Trypan blue. Apoptosis and senescence were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and senescence-associated β-galactosidase (SA-β-gal) staining, respectively. The expression of cleaved caspase-3, Bax, p53 and p21 was analyzed by western blotting. Clonogenic survival assays demonstrated a synergistic radiosensitizing effect of carboplatin and paclitaxel with carbon-ion beams; the sensitizer enhancement ratios (SERs) at the dose giving a 10% survival fraction (D10) were 1.21 and 1.22, respectively. Similarly, carboplatin and paclitaxel showed a radiosensitizing effect with X-rays; the SERs were 1.41 and 1.29, respectively. Cell proliferation assays validated the radiosensitizing effect of carboplatin and paclitaxel with both carbon-ion beam and X-ray irradiation. Carboplatin and paclitaxel treatment combined with carbon-ion beams increased TUNEL-positive cells and the expression of cleaved caspase-3 and Bax, indicating the enhancement of apoptosis. The combined treatment also increased SA-β-gal-positive cells and the expression of p53 and p21, indicating the enhancement of senescence. In summary, carboplatin and paclitaxel radiosensitized H460 cells to carbon-ion beam irradiation by enhancing irradiation-induced apoptosis and senescence.
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影响因子：
5.2
作者：
Ohno T;Kanai T;Yamada S;Yusa K;Tashiro M;Shimada H;Torikai K;Yoshida Y;Kitada Y;Katoh H;Ishii T;Nakano T
通讯作者：
Nakano T
影响因子：
158.5
作者：
DILLMAN, RO;SEAGREN, SL;GREEN, MR
通讯作者：
GREEN, MR
影响因子：
3.4
作者：
Ito, A;Nakano, H;Shinohara, K
通讯作者：
Shinohara, K
影响因子：
2.6
作者：
Combs, Stephanie E.;Bohl, Jessica;Weyrather, Wilma K.
通讯作者：
Weyrather, Wilma K.
影响因子：
3.6
作者：
Carter, Dennis L.;Garfield, David;Reynolds, Craig
通讯作者：
Reynolds, Craig