沉默 Prx1 和/或 Prx5 可使人类食管癌细胞对电离辐射敏感，并通过细胞内 ROS 积累增加细胞凋亡。
Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation.
机构信息
Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
出版信息
Acta Pharmacol Sin. 2011 Apr;32(4):528-36. doi: 10.1038/aps.2010.235.
AIM
To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR).
METHODS
Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo.
RESULTS
Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR.
CONCLUSION
Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.
目的
研究过氧化物还原酶 1（Prx1）和/或过氧化物还原酶 5（Prx5）下调是否使人类食管癌细胞对电离辐射（IR）敏感。
方法
使用人食管癌细胞系 Eca-109 和 TE-1。采用 RT-PCR 测定 Eca-109 和 TE-1 细胞中 Prx mRNA 的表达谱。用 RNA 干扰（RNAi）沉默两种高表达的 Prx 同工型，Prx1 和 Prx5。用流式细胞术测量 IR 后细胞内活性氧（ROS）和细胞凋亡，测量过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，并观察 RNAi 的放射增敏作用。还使用肿瘤异种移植模型在体内研究 RNAi 的放射增敏作用。
结果
RNAi 下调 Prx1 和/或 Prx5 不会改变过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，但使人类肿瘤细胞对 IR 诱导的凋亡更加敏感，无论是在体外还是体内。当两种同工型同时减少时，IR 后细胞内 ROS 和凋亡显著增加。
结论
用 RNAi 沉默 Prx1 和/或 Prx5 可使人类 Eca-109 和 TE-1 细胞对 IR 敏感，细胞内 ROS 积累可能有助于 RNAi 的放射增敏作用。
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