Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.
Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.
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木犀草素通过调节 MicroRNA-34a-5p 抑制肿瘤发生并诱导非小细胞肺癌细胞凋亡
DOI：
10.3390/ijms19020447
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发表时间：
2018-02-02
影响因子：
5.6
通讯作者：
Wu MH
中科院分区：
文献类型：
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作者：
Jiang ZQ;Li MH;Qin YM;Jiang HY;Zhang X;Wu MH
木犀草素（LTL）对包括非小细胞肺癌（NSCLC）在内的多种癌症具有显著的肿瘤抑制活性。然而，其对NSCLC的作用机制是否与microRNAs（miRNAs）有关尚不完全清楚。在本研究中，我们研究了LTL在体外和体内对NSCLC的抗肿瘤作用。结果表明，LTL能抑制A549和H460细胞的增殖并诱导其凋亡。在裸鼠H460异种移植瘤模型中，LTL显著抑制肿瘤生长，抑制细胞增殖，并诱导凋亡。miRNA微阵列和定量PCR（qPCR）分析表明，在肿瘤组织中，miR-34a-5p在LTL处理后显著上调。荧光素酶报告基因检测证实MDM4是miR-34a-5p的直接靶点。LTL治疗与NSCLC细胞和肿瘤组织中p53和p21蛋白表达增加以及MDM4蛋白表达降低相关。当miR-34a-5p在体外被抑制时，Bcl-2和MDM4的蛋白表达恢复，而p53、p21和Bax的蛋白表达减弱。此外，miR-34a-5p抑制也抑制了体外LHL处理诱导的caspase-3和caspase-9活化。总体而言，LTL可以通过靶向MDM4上调miR-34a-5p来抑制肿瘤发生并诱导NSCLC细胞凋亡。这些发现为LTL的分子功能提供了新的见解，表明其作为人类NSCLC治疗剂的潜力。
Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.
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影响因子：
--
作者：
Brentnall M;Rodriguez-Menocal L;De Guevara RL;Cepero E;Boise LH
通讯作者：
Boise LH
DOI：
10.1007/978-3-319-24932-2_8
发表时间：
2016-01-01
期刊：
LUNG CANCER AND PERSONALIZED MEDICINE: NOVEL THERAPIES AND CLINICAL MANAGEMENT
影响因子：
--
作者：
Hussain, Sajid
通讯作者：
Hussain, Sajid
木犀草素诱导非小细胞肺癌细胞G2期细胞周期停滞和细胞凋亡
影响因子：
3.2
作者：
Cai, Xueting;Ye, Tingmei;Cao, Peng
通讯作者：
Cao, Peng
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1016/j.bbrc.2016.01.002
发表时间：
2016-01-29
影响因子：
3.1
作者：
Choi, Hee-Jin;Choi, Hee-Jung;Ha, Ki-Tae
通讯作者：
Ha, Ki-Tae