Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy.
Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy.
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DOI：
10.1038/cddis.2011.56
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发表时间：
2011-06-30
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
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放射疗法是一种公认的癌症治疗方法。然而，放射抵抗细胞的存在是放射治疗的主要障碍之一。为了理解细胞辐射抗性的机制并开发更有效的放射治疗，我们建立了临床相关的辐射抗性（CRR）细胞系，其在每天暴露于2戈瑞（戈伊）的X射线下持续增殖>30天。X射线照射显着诱导亲代细胞中的自噬细胞，而在CRR细胞中这种自噬细胞很少，表明自噬细胞死亡与细胞的辐射敏感性有关。自噬诱导剂雷帕霉素使CRR细胞敏感至亲本细胞的水平并抑制细胞生长。自噬抑制剂3-甲基腺嘌呤诱导亲本细胞的辐射抗性。此外，通过敲低Beclin-1抑制自噬使亲本细胞对急性辐射具有辐射抗性。这些结果表明，细胞辐射抗性主要涉及对自噬性细胞死亡的抑制，而不是凋亡。因此，增强自噬可能对放射抵抗性肿瘤的治疗产生相当大的影响。
Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.
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影响因子：
2
作者：
Kuwahara, Yoshikazu;Mori, Miyuki;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu
影响因子：
5.7
作者：
Kuwahara, Yoshikazu;Li, Li;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu
影响因子：
13.3
作者：
Dalby KN;Tekedereli I;Lopez-Berestein G;Ozpolat B
通讯作者：
Ozpolat B
影响因子：
3.7
作者：
Bauvy, C;Gane, P;Ogier-Denis, E
通讯作者：
Ogier-Denis, E
影响因子：
12.4
作者：
Kanzawa, T;Germano, IM;Kondo, S
通讯作者：
Kondo, S