Chloroquine Sensitizes Nasopharyngeal Carcinoma Cells but Not Nasoepithelial Cells to Irradiation by Blocking Autophagy.
Chloroquine Sensitizes Nasopharyngeal Carcinoma Cells but Not Nasoepithelial Cells to Irradiation by Blocking Autophagy.
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DOI：
10.1371/journal.pone.0166766
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kontny U
中科院分区：
文献类型：
--
作者：
Makowska A;Eble M;Prescher K;Hoß M;Kontny U
鼻咽癌的治疗需要使用高剂量的辐射，导致大多数患者出现严重的长期并发症。使肿瘤细胞对放射敏感可能是增加放射治疗窗口期的一种手段。鼻咽癌细胞显示自噬的改变和自噬的阻断已被证明对化疗敏感。我们在5个鼻咽癌细胞系和一个sv40转化的鼻上皮细胞系中研究了氯喹（一种已知的自噬抑制剂）对辐射诱导的细胞凋亡致敏的影响。采用自噬相关蛋白免疫印迹、自噬体微泡免疫荧光和电镜检测自噬情况。通过siRNA抑制自噬相关蛋白3、5、6和7 （ATG3、ATG5、ATG6和ATG7）阻断自噬。氯喹使五种鼻咽癌细胞系中的四种对辐射诱导的细胞凋亡敏感。特异性siRNA对ATG3、ATG5、ATG6和ATG7的抑制作用可替代氯喹的作用，致敏作用是基于阻断自噬作用。鼻上皮细胞未见致敏。氯喹通过阻断鼻咽癌细胞自噬使鼻咽癌细胞对辐射诱导的细胞凋亡增敏，但对鼻上皮细胞无增敏作用。在小鼠异种移植物模型中进一步的研究有理由在体内证实这种效果。
Treatment of nasopharyngeal carcinoma requires the application of high dosages of radiation, leading to severe long-term complications in the majority of patients. Sensitizing tumor cells to radiation could be a means to increase the therapeutic window of radiation. Nasopharyngeal carcinoma cells display alterations in autophagy and blockade of autophagy has been shown to sensitize them against chemotherapy. We investigated the effect of chloroquine, a known inhibitor of autophagy, on sensitization against radiation-induced apoptosis in a panel of five nasopharyngeal carcinoma cell lines and a SV40-transformed nasoepithelial cell line. Autophagy was measured by immunoblot of autophagy-related proteins, immunofluorescence of autophagosomic microvesicles and electron microscopy. Autophagy was blocked by siRNA against autophagy-related proteins 3, 5, 6 and 7 (ATG3, ATG5, ATG6 and ATG7). Chloroquine sensitized four out of five nasopharyngeal cancer cell lines towards radiation-induced apoptosis. The sensitizing effect was based on the blockade of autophagy as inhibition of ATG3, ATG5, ATG6 and ATG7 by specific siRNA could substitute for the effect of chloroquine. No sensitization was seen in nasoepithelial cells. Chloroquine sensitizes nasopharyngeal carcinoma cells but not nasoepithelial cells towards radiation-induced apoptosis by blocking autophagy. Further studies in a mouse-xenograft model are warranted to substantiate this effect in vivo.
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DOI：
10.1158/1078-0432.ccr-13-3227
发表时间：
2014-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cook KL;Wärri A;Soto-Pantoja DR;Clarke PA;Cruz MI;Zwart A;Clarke R
通讯作者：
Clarke R
影响因子：
8.4
作者：
Li, Jie;Hou, Ni;Kuwano, Hiroyuki
通讯作者：
Kuwano, Hiroyuki
影响因子：
11.2
作者：
Apel, Anja;Herr, Ingrid;Mayer, Andreas
通讯作者：
Mayer, Andreas
影响因子：
4.2
作者：
Du, Hailei;Yang, Weiping;Qiu, Weihua
通讯作者：
Qiu, Weihua
影响因子：
3.7
作者：
Al Dhaheri Y;Attoub S;Ramadan G;Arafat K;Bajbouj K;Karuvantevida N;AbuQamar S;Eid A;Iratni R
通讯作者：
Iratni R