All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction.
All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction.
复制标题
全反式视黄酸通过连接蛋白 43 介导的间隙连接增加细胞间通讯，从而阻止白血病骨髓基质细胞的细胞周期。
DOI：
10.1186/s13045-015-0212-7
复制
发表时间：
2015-10-07
影响因子：
28.5
通讯作者：
Zhong JF
中科院分区：
文献类型：
--
作者：
Liu Y;Wen Q;Chen XL;Yang SJ;Gao L;Gao L;Zhang C;Li JL;Xiang XX;Wan K;Chen XH;Zhang X;Zhong JF
恶性肿瘤中间隙连接细胞间通讯（GJIC）通常会减少。间隙连接不存在于造血细胞之间，而是存在于骨髓基质细胞（BMSC）中。连接蛋白 43 (Cx43) 是主要的间隙连接 (GJ) 蛋白；我们之前的研究表明，急性白血病 BMSC 中 Cx43 表达和 GJIC 降低。全反式维甲酸（ATRA）可增加多种癌细胞中的GJIC，并已用于治疗急性早幼粒细胞白血病，但ATRA对白血病BMSCs的影响尚不清楚。在本研究中，我们评估了 ATRA 对白血病 BMSC 的细胞周期、增殖和凋亡的潜在影响。还检查了 ATRA 对 Cx43 表达和 GJIC 的影响。培养取自 25 名原发性急性白血病患者和 10 名正常健康供体的人 BMSC。在与或不与两性霉素-B 共同处理的情况下检查 ATRA 对细胞周期、细胞增殖和凋亡的影响。在 mRNA 和蛋白质表达水平上检查了 Cx43 的表达。通过使用染料转移测定并测量光漂白后荧光恢复率 (FRAP) 来检查 GJIC。 ATRA 可阻止白血病 BMSC 的细胞周期进程、抑制细胞生长并增加细胞凋亡。 ATRA 处理后 Cx43 表达和 GJIC 功能均增加。大部分观察到的 ATRA 介导的作用均被两性霉素 B 预处理所消除。 ATRA 可阻止白血病 BMSC 中的细胞周期进程，这可能是由于上调 Cx43 表达并增强 GJIC 功能所致。本文的在线版本 (doi:10.1186/s13045-015-0212-7) 包含补充材料，可供授权用户使用。
Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined. Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP). ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment. ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function. The online version of this article (doi:10.1186/s13045-015-0212-7) contains supplementary material, which is available to authorized users.