Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway.
Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway.
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DOI：
10.2147/ijn.s83838
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发表时间：
2015
影响因子：
8
通讯作者：
Wu JZ
中科院分区：
文献类型：
--
作者：
Wang H;Liu Z;Gou Y;Qin Y;Xu Y;Liu J;Wu JZ
雄黄(AS4S4)已被用于治疗癌症的传统药物，但其较差的水溶性仍然是其临床应用的主要障碍。因此，合成了具有更好的水溶性和生物利用度的雄黄量子点。采用四甲基偶氮唑盐比色法、透射电子显微镜、流式细胞仪、实时逆转录聚合酶链式反应和Western印迹分析等方法，观察不同浓度RQDS对人子宫内膜癌JEC细胞的抑制作用，并探讨其作用机制。结果表明，所制备的RQD的最高光致发光量子产率约为70%，平均尺寸为5.48 nm。RQDS以浓度依赖的方式诱导对JEC细胞的抗增殖活性。在光镜和透射电子显微镜下，RQD以浓度依赖的方式诱导JEC细胞空泡化和内质网扩张。GADD153和GRP78在mRNA和蛋白水平的表达均增加，进一步证实了RQD诱导的内质网应激。流式细胞仪和线粒体膜电位检测显示，内质网应激进一步导致JEC细胞凋亡和坏死。我们的研究结果表明，新合成的RQD对人子宫内膜癌细胞具有有效的抑制作用。潜在的机制似乎是，至少部分是由于内质网应激导致细胞凋亡和坏死。
Realgar (AS4S4) has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs) were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM), flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antipro-liferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER) dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis.