Liu Baorong, Yuan Bo, Zhang Lan, Mu Weimin, Wang Chongmin
Second Division of Department of General Surgery, Xi'an Central Hospital Shaanxi, China.
Department of General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University Shaanxi, China.
Int J Clin Exp Med. 2015 Sep 15;8(9):15413-22. eCollection 2015.
Emodin was found effective in suppressing proliferation of cancer cells including colorectal cancer (CRC), but the mechanisms were still unclear. This study was aimed to investigate the possible mechanism of emodin's anti-CRC effects.
Two most frequently used CRC cell lines, SW480 and SW620, were investigated in this study. Serially diluted emodin solutions were used to incubate CRC cells. siRNAs were used to silence the expressions of p38 and Puma respectively. Intracellular ROS production was detected by DCFH-DA staining; proliferation and apoptosis of CRC cells were assessed by MTT assay and Hoechst staining respectively. Western blotting was applied to evaluate the activation of p38/p53/Puma signaling.
Both in SW480 and SW620 cells, emodin inhibited proliferation by inducing ROS-mediated apoptosis in a concentration-dependent manner. The p38/p53/Puma signaling was also activated after emodin incubation in a concentration-dependent manner. The ROS scavenger NAC, p38 silencing and Puma silencing impaired the anti-proliferation and apoptosis- inducing effects of emodin.
emodin inhibited proliferation of human CRC cells by inducing cell apoptosis by activating ROS/p38/p53/Puma signaling.
已发现大黄素对包括结直肠癌（CRC）在内的癌细胞增殖具有抑制作用，但其机制尚不清楚。本研究旨在探讨大黄素抗结直肠癌作用的可能机制。
本研究选用两种最常用的结直肠癌细胞系SW480和SW620。用系列稀释的大黄素溶液孵育结直肠癌细胞。分别使用小干扰RNA（siRNAs）沉默p38和Puma的表达。通过2′,7′-二氯二氢荧光素二乙酸酯（DCFH-DA）染色检测细胞内活性氧（ROS）的产生；分别通过噻唑蓝（MTT）法和 Hoechst 染色评估结直肠癌细胞的增殖和凋亡情况。采用蛋白质免疫印迹法评估p38/p53/Puma信号通路的激活情况。
在SW480和SW620细胞中，大黄素均以浓度依赖的方式通过诱导ROS介导的细胞凋亡抑制细胞增殖。大黄素孵育后，p38/p53/Puma信号通路也以浓度依赖的方式被激活。ROS清除剂N-乙酰半胱氨酸（NAC）、p38沉默和Puma沉默均削弱了大黄素的抗增殖和诱导凋亡作用。
大黄素通过激活ROS/p38/p53/Puma信号通路诱导细胞凋亡，从而抑制人结直肠癌细胞的增殖。
