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腺病毒介导的白细胞介素-24在体外和体内均赋予人肺腺癌放射敏感性。

Adenovirus-mediated IL-24 confers radiosensitization to human lung adenocarcinoma in vitro and in vivo.

作者信息

Zheng Shi-Ying, Ge Jin-Feng, Zhao Jun, Jiang Dong, Li Fang

机构信息

Department of Thoracocardiac Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China,

出版信息

Mol Biol Rep. 2015 Jun;42(6):1069-80. doi: 10.1007/s11033-014-3846-6. Epub 2014 Dec 6.

DOI:10.1007/s11033-014-3846-6
PMID:25479732
Abstract

The current paper aims to study the effect of adenovirus-mediated IL-24 (Ad-IL-24) on human lung adenocarcinoma in vitro and in vivo and determine its possible mechanism of action. The growth-suppressing and apoptosis-inducing effects of Ad-IL-24, radiotherapy, and Ad-IL-24+ radiotherapy (hereinafter referred to as the joint group) on SPC-A1 lung carcinoma cells were assessed by using 3-(4,5-dimethyliazolyl-2)-2,5-diphnyltetrazolium bromide and flow cytometry. A human lung model was established with SPC-A1 cells in nude mice. Groups of mice were subjected to multi-point injections to their tumors. Gross tumor volumes were measured dynamically. The ratios of tumor suppression and radiosensitization effect were evaluated according to the method of probability sum Q values. The expressions of Bax, Bcl-2, Survivin, and Caspase-3 in tumor samples were detected by immunohistochemistry. The ratios of inhibition and apoptosis in the joint group were higher than those in the individual Ad-IL-24 and radiotherapy groups. In vitro, the joint group suppressed tumor growth conspicuously, showing a weight inhibition rate of about 64 %. The expressions of FasL, Bax and Caspase-3 were upregulated in the joint group, while the expressions of Cox,Bcl-2,VEGF,CD34 and Survivin were downregulated. The current study proves that Ad-IL-24 suppresses growth of SPC-A1 cells both in vitro and in vivo. Its functions appear to be related to cell apoptosis and antiangiogenesis.

摘要

本论文旨在研究腺病毒介导的白细胞介素-24(Ad-IL-24)在体外和体内对人肺腺癌的作用,并确定其可能的作用机制。采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐和流式细胞术评估Ad-IL-24、放射治疗以及Ad-IL-24+放射治疗(以下简称联合组)对SPC-A1肺癌细胞的生长抑制和凋亡诱导作用。用SPC-A1细胞在裸鼠体内建立人肺模型。对小鼠分组并对其肿瘤进行多点注射。动态测量肿瘤总体积。根据概率和Q值法评估肿瘤抑制率和放射增敏效果。通过免疫组织化学检测肿瘤样本中Bax、Bcl-2、Survivin和Caspase-3的表达。联合组的抑制率和凋亡率高于单独的Ad-IL-24组和放射治疗组。在体外,联合组显著抑制肿瘤生长,重量抑制率约为64%。联合组中FasL、Bax和Caspase-3的表达上调,而Cox、Bcl-2、VEGF、CD34和Survivin的表达下调。本研究证明Ad-IL-24在体外和体内均能抑制SPC-A1细胞的生长。其作用似乎与细胞凋亡和抗血管生成有关。

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IL-24 induces apoptosis of chronic lymphocytic leukemia B cells engaged into the cell cycle through dephosphorylation of STAT3 and stabilization of p53 expression.白细胞介素-24通过使信号转导子和转录激活子3(STAT3)去磷酸化以及稳定p53表达,诱导进入细胞周期的慢性淋巴细胞白血病B细胞凋亡。
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