大黄素对HCT116结肠癌细胞凋亡作用及机制研究

张昊悦; 赵蓓; 章阳

大黄素对HCT116结肠癌细胞凋亡作用及机制研究

1.
南京中医药大学附属南京中医院，江苏南京 210001
2.
上海中医药大学附属岳阳中西医结合医院，上海 200437

计量
- 文章访问数: 625
- HTML全文浏览量: 5
- PDF下载量: 494
- 被引次数: 0
出版历程
- 刊出日期: 2020-07-10

Effect and Mechanism of Emodin on Apoptosis and Cycle of HCT116 Cells

1.
Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210001, China
2.
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China

摘要

摘要: 目的研究大黄素促进人结肠癌细胞HCT116细胞凋亡的作用及其分子机制。方法通过CCK8法检测大黄素对细胞活力的影响，并计算出IC₅₀。Annexin-V/PI流式细胞术检测细胞凋亡，流式细胞术检测细胞周期和荧光探针DCF-DA细胞内活性氧(ROS)的水平，Western blot法检测Bax、Bcl-2、p-ERK1/2、ERK1/2和c-Myc的表达。结果不同浓度的大黄素抑制HCT116细胞的活力，并且具有浓度依赖性。大黄素将HCT116细胞周期阻滞在G0/G1期(P<0.05)，并且能够明显诱导ROS的产生(P<0.01)，Western blot结果显示大黄素能够引起Bax/Bcl-2表达的上调，p-ERK1/2和c-Myc表达的降低(P<0.05)。结论大黄素可以通过上调Bax/Bcl-2，下调c-Myc和p-ERK/ERK的表达从而促进结肠癌细胞的凋亡，阻滞细胞周期和增加ROS的产生。
- 大黄素 /
- 凋亡 /
- 活性氧 /
- HCT116细胞 /
- c-Myc
Abstract: OBJECTIVE To investigate the effect of emodin on human colon cancer cell line HCT116 and its molecular mechanism. METHODS The inhibitory effects of emodin on the viability of HCT116 cells were measured by CCK8 assay. Apoptosis rates of HCT116 cells were determined by flow cytometry. The cell cycle and the level of reactive oxygen species (ROS) in the fluorescent probe DCF-DA were detected by flow cytometry. The protein levels of Bax，Bcl-2，p-ERK1/2，ERK1/2 and c-Myc were determined by Western blot. RESULTS Treatment with emodin of 0， 25， 50， 100， 200， 300 μmol/L for 24 h significantly reduced the viability of HCT116 cells. Emodin promoted the apoptosis of HCT116 cells， blocked cell growth cycle in G0/G1 phase and induced the production of ROS， significantly. Western blot results showed that emodin promoted the up-regulation of Bax/Bcl-2 expression and inhibited the expression of c-Myc and p-ERK/ERK. CONCLUSION Emodin inhibits the proliferation of HCT116 cells， promotes cell apoptosis， induces cell cycle arrest in G1/G0 phase and ROS production， by promoting Bax/Bcl-2 expression and inhibiting c-Myc， p-ERK/ERK expression.
- emodin /
- apoptosis /
- ROS /
- HCT116 cells /
- c-Myc

HTML全文

参考文献(20)

[1]	MILLER KD，NOGUEIRA L，MARIOTTO AB，et al．Cancer treatment and survivorship statistics，2019[J]．CA Cancer J Clin，2019，69(5)：363-385．
[2]	李中辉，董旺，陈敏，等.大黄素下调ILK/PI3K/Akt信号通路抑制结肠癌CACO-2细胞增殖的机制研究[J].今日药学，2020，30(2):116-120.
[3]	MA QZ，DING YQ，WU ZQ，et al．Antitumor effects of emodin in CACO-2 human colon carcinoma cells are mediated via apoptosis，cell cycle arrest and downregulation of PI3K/AKT signalling pathway[J]．J BUON，2018，23(3)：587-591．
[4]	SAUNDERS IT，MIR H，KAPUR N，et al．Emodin inhibits colon cancer by altering BCL-2 family proteins and cell survival pathways[J]．Cancer Cell Int，2019，19：98．
[5]	GU J，CUI CF，YANG L，et al．Emodin inhibits colon cancer cell invasion and migration by suppressing epithelial-mesenchymal transition via the wnt/β-catenin pathway[J]．Oncol Res，2019，27(2)：193-202．
[6]	郑婕．蒽醌类衍生物C3通过ERK1/2-ERCC1信号通路对结肠癌细胞影响的研究[D]．太原：山西大学，2019．
[7]	林玩福，汪晨，凌昌全．大黄素抗肿瘤作用研究进展[J]．中国中药杂志，2015，40(20)：3937-3940．
[8]	TRYBUS W，KRL T，TRYBUS E，et al．Emodin induces death in human cervical cancer cells through mitotic catastrophe[J]．Anticancer Res，2019，39(2)：679-686．
[9]	〖JP2〗DONG X，NI BR，FU J，et al．Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase-dependent pathway[J]．Oncol Rep，2018，40(4)：1985-1993．〖JP〗
[10]	WANG YY，LUO Q，HE XL，et al．Emodin induces apoptosis of colon cancer cells via induction of autophagy in a ROS-dependent manner[J]．Oncol Res，2018，26(6)：889-899．
[11]	DONG X， NI B， FU J， et al. Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase-dependent pathway[J]. Oncol Rep， 2018， 40: 1985-1993.
[12]	LUNA-VARGAS MPA， CHIPUK JE. Physiological and pharmacological control of BAK， BAX， and beyond[J]. Trends Cell Biol，2016，26(12): 906-917.
[13]	龚张斌，徐品初，金国琴．左归丸对大鼠胸腺细胞凋亡及Bcl-2，Bax表达的影响[J]．中国老年学杂志，2010，30(22)：3290-3292．
[14]	GILL JG，PISKOUNOVA E，MORRISON SJ．Cancer，oxidative stress，and metastasis[J]．Cold Spring Harb Symp Quant Biol，2016，81(1)：163-175．
[15]	GAN XQ，HUANG SB，WU L，et al．Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer's disease cybrid cell[J]．Biochim Biophys Acta，2014，1842(2)：220-231．
[16]	〖JP2〗PYAKUREL A，SAVOIA C，HESS D，et al．Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis[J]．Mol Cell，2015，58(2)：244-254．〖JP〗
[17]	WANG D，XU Y，FENG L，et al．RGS5 decreases the proliferation of human ovarian carcinoma-derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia[J]．Oncol Rep，2018，41(1)：165-177．
[18]	〖JP2〗PYAKUREL A，SAVOIA C，HESS D，et al．Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis[J]．Mol Cell，2015，58(2)：244-254．〖JP〗
[19]	LEE WD，MUKHA D，AIZENSHTEIN E，et al．Spatial-fluxomics provides a subcellular-compartmentalized view of reductive glutamine metabolism in cancer cells[J]．Nat Commun，2019，10(1)：1351．
[20]	ZHAO HX，LI T，WANG K，et al．AMPK-mediated activation of MCU stimulates mitochondrial Ca²⁺ entry to promote mitotic progression[J]．Nat Cell Biol，2019，21(4)：476-486．