[1]谢家印,王东,李梦侠,等.APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6及IL-8分泌的体外研究[J].第三军医大学学报,2009,31(19):1850-1853.
 XIE Jia-yin,WANG Dong,LI Meng-xia,et al.APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients[J].J Third Mil Med Univ,2009,31(19):1850-1853.
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APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6及IL-8分泌的体外研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
31卷
期数:
2009年第19期
页码:
1850-1853
栏目:
论著
出版日期:
2009-10-15

文章信息/Info

Title:
APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients
作者:
谢家印王东李梦侠向德兵杨镇洲杨宇馨李增鹏曾林立仲召阳王阁
第三军医大学大坪医院野战外科研究所肿瘤中心
Author(s):
XIE Jia-yin WANG Dong LI Meng-xia XIANG De-bing YANG Zhen-zhou YANG Yu-xin LI Zeng-peng ZENG Lin-li ZHONG Zhao-yang WANG Ge
Cancer Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
关键词:
多发性骨髓瘤骨髓基质细胞RNA干扰白细胞介素-6白细胞介素-8
Keywords:
multiple myeloma bone marrow stromal cellsapurinic/apyrimidinic endonuclease 1/redox factor-1 interleukin-8interleukin-6
分类号:
R392.11;R394.3;R733.3
文献标志码:
A
摘要:
目的   体外通过APE1/Ref-1 siRNA敲低多发性骨髓瘤骨髓基质细胞(bone marrow stromal cells,BMSCs) APE1/Ref-1的表达,观察BMSCs的增殖及分泌细胞因子IL-6、IL-8的变化,初步探讨BMSCs APE1/Ref-1表达的功能特点。   方法   通过免疫细胞化学染色法定量检测35例初治、11例复发/难治多发性骨髓瘤患者及10例正常人BMSCs APE1/Ref-1的表达特点及其差异,经Adv5-APE1/Ref-1 siRNA感染BMSCs后,流式细胞仪检测BMSCs细胞周期的变化;ELISA法检测BMSCs分泌IL-6、IL-8的水平变化情况。   结果   多发性骨髓瘤BMSCs的APE1/Ref-1蛋白阳性表达率显著高于正常BMSCs APE1/Ref-1蛋白阳性表达率(P<0.05),且多发性骨髓瘤BMSCs的APE1/Ref-1呈细胞核及核浆共同表达方式。Adv5-APE1/Ref-1 siRNA感染敲低多发性骨髓瘤及正常BMSCs APE1/Ref-1的表达量呈进行性减少 (P<0.01),同时发现APE1/Ref-1 siRNA对多发性骨髓瘤BMSCs抑制作用更明显。Adv5-APE1/Ref-1 siRNA感染BMSCs 后对正常人及骨髓瘤患者BMSCs分泌细胞因子IL-6、IL-8的量有显著的抑制作用,特别是感染72 h后,骨髓瘤患者及正常人的BMSCs 分泌IL-6[初治患者(246.29±46.51)pg/ml,复发/难治患者(365.09±75.25)pg/ml]、IL-8[初治患者(118.77±18.08) pg/ml,复发/难治患者(188.71±33.76)pg/ml]的量最低,与其他时段比较差异有统计学意义(P<0.01)。   结论   多发性骨髓瘤BMSCs APE1/Ref-1的表达特点不同于正常BMSCs,可能导致其功能差异;APE1/Ref-1 siRNA敲低了MM BMSCs APE1/Ref-1的表达,同时明显抑制了其IL-6、IL-8的分泌,减少了对骨髓瘤细胞的促增殖和凋亡作用。
Abstract:
Objective   To explore the possible roles of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) expression in the bone marrow stromal cells (BMSCs) form multiple myeloma (MM) patients.    Methods   The expression of APE1/Ref-1 protein in BMSCs isolated from the bone marrow samples of 35 initial cases, 11 relapse/refractory cases with MM and 10 cases health individuals were detected by immunocytochemistry. Before and after the transfection of the adenoviral vector Adv5-APE1/Ref-1 siRNA, the concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8) in the supernatant of BMSCs were measured with ELISA, and the cell cycles proliferation of BMSCs were detected with flow cytometry.    Results   The expression of APE1/Ref-1 protein in the cultured BMSCs was significantly higher than in normal BMSCs (P<0.05). APE1/Ref-1 siRNA obviously inhibited the expression of the protein in MM or normal BMSCs. Transfected with Adv5-APE1/Ref-1 siRNA, the MM or normal BMSCs gradually decreased the levels of IL-6 and IL-8 secretion in a time course. In 72 h after the transfection, the amounts of IL-6 and IL-8 in the BMSCs supernatant reached the lowest levels as following, IL-6 (246.29±46.51) pg/ml and IL-8 (118.77±18.08) pg/ml in initial MM group, and IL-6 (365.09±75.25) pg/ml and IL-8 (188.71±33.76) pg/ml in relapse/refractory group (P<0.01).    Conclusion   The abnormal expression of APE1/Ref-1 protein in MM BMSCs may lead to many changes of biological function. APE1/Ref-1 siRNA knocks down the expression of APE1/Ref-1 protein in BMSCs, and inhibits the production of IL-6 and IL-8 in MM BMSCs, thus indirectly reduces the proliferation or benefit apoptosis of myeloma cells.

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更新日期/Last Update: 2009-09-29