Combination effect of epigenetic regulation and ionizing radiation in colorectal cancer cells.
Combination effect of epigenetic regulation and ionizing radiation in colorectal cancer cells.
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DOI：
10.1371/journal.pone.0105405
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yi JM
中科院分区：
文献类型：
--
作者：
Kim JG;Bae JH;Kim JA;Heo K;Yang K;Yi JM
细胞暴露在电离辐射(IR)中，不仅能激活决定细胞命运的多条信号通路，而且还能改变参与细胞死亡或存活的分子通路。最近，DNA甲基化被证实是参与肿瘤细胞基因表达调控的关键表观遗传过程，提示抑制DNA甲基化可能是一种有效的癌症治疗策略。由于DNA甲基化引起的基因表达改变被认为影响放射反应，因此我们研究了DNA甲基转移酶抑制剂5-氮杂-2‘-脱氧胞苷(5-aza-2’-deoxcytidine，5-aza-DC)对放射敏感性的影响。此外，我们还研究了电离辐射(IR)和5-氮杂胞苷(5-aza-DC)联合作用于人结肠癌细胞的潜在细胞机制。首先用红外光谱检测结肠癌细胞系的放射敏感性，然后用两种不同剂量的5-氮杂-树突状细胞处理。采用四甲基偶氮唑盐比色法((3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)和克隆形成法检测细胞存活率。观察5-氮杂-树突状细胞(5-aza-DC)联合照射对细胞生长、细胞周期分布、细胞凋亡及相关基因表达的影响。与单独照射或单独照射相比，5-氮杂胞苷与5-氮杂胞苷联合照射显著降低生长活性。照射联合5-aza-DC处理后，HCT116细胞处于亚G1期的百分率和凋亡率均明显高于单独照射组。Caspase活性增加，彗星分析彗星尾数增加，以及凋亡相关分子(caspase 3/9，裂解PARP)的蛋白水平增加，有力地支持了这些观察结果。我们的研究结果表明，5-氮杂胞苷增强了结肠癌细胞的放射敏感性，并且5-氮杂胞苷与放疗的联合作用比单一治疗显示出更大的细胞效应，提示5-氮杂胞苷与放疗的联合应用有可能成为治疗癌症的一种临床策略。
Exposure of cells to ionizing radiation (IR) induces, not only, activation of multiple signaling pathways that play critical roles in cell fate determination, but also alteration of molecular pathways involved in cell death or survival. Recently, DNA methylation has been established as a critical epigenetic process involved in the regulation of gene expression in cancer cells, suggesting that DNA methylation inhibition may be an effective cancer treatment strategy. Because alterations of gene expression by DNA methylation have been considered to influence radioresponsiveness, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC), on radiosensitivity. In addition, we investigated the underlying cellular mechanisms of combination treatments of ionizing irradiation (IR) and 5-aza-dC in human colon cancer cells. Colon cancer cell lines were initially tested for radiation sensitivity by IR in vitro and were treated with two different doses of 5-aza-dC. Survival of these cell lines was measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays. The effects of 5-aza-dC along with irradiation on cell growth, cell cycle distribution, apoptosis, and apoptosis-related gene expression were examined. Combination irradiation treatment with 5-aza-dC significantly decreased growth activity compared with irradiation treatment alone or with 5-aza-dC treatment alone. The percentage of HCT116 cells in the sub-G1 phase and their apoptotic rate was increased when cells were treated with irradiation in combination with 5-aza-dC compared with either treatment alone. These observations were strongly supported by increased caspase activity, increased comet tails using comet assays, and increased protein levels of apoptosis-associated molecules (caspase 3/9, cleaved PARP). Our data demonstrated that 5-aza-dC enhanced radiosensitivity in colon cancer cells, and the combination effects of 5-aza-dC with radiation showed greater cellular effects than that of single treatment, suggesting that the combination of 5-aza-dC and radiation has the potential to become a clinical strategy for the treatment of cancer.
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影响因子：
2.6
作者：
GOODHEAD, DT
通讯作者：
GOODHEAD, DT
影响因子：
4.5
作者：
Schuebel KE;Chen W;Cope L;Glöckner SC;Suzuki H;Yi JM;Chan TA;Van Neste L;Van Criekinge W;van den Bosch S;van Engeland M;Ting AH;Jair K;Yu W;Toyota M;Imai K;Ahuja N;Herman JG;Baylin SB
通讯作者：
Baylin SB
影响因子：
56.9
作者：
Lakhani, SA;Masud, A;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1016/0277-5379(87)90060-5
发表时间：
1987-12-01
期刊：
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY
影响因子：
--
作者：
ABELE, R;CLAVEL, M;PINEDO, HM
通讯作者：
PINEDO, HM
影响因子：
11.5
作者：
Dote, H;Cerna, D;Tofilon, PJ
通讯作者：
Tofilon, PJ