19-Hydroxybufalin inhibits non-small cell lung cancer cell proliferation and promotes cell apoptosis via the Wnt/β-catenin pathway.
19-Hydroxybufalin inhibits non-small cell lung cancer cell proliferation and promotes cell apoptosis via the Wnt/β-catenin pathway.
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DOI：
10.1186/s40164-021-00243-0
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发表时间：
2021-10-25
影响因子：
10.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Yu W;Zhang X;Zhang W;Xiong M;Lin Y;Chang M;Xu L;Lu Y;Liu Y;Zhang J
从蟾蜍皮肤中提取的蟾二烯内酯常被认为是具有抗肿瘤作用的主要活性成分。19-羟基蟾毒灵（19-HB）是蟾毒二烯内酯的单体；然而，其对肿瘤生长的影响和潜在的分子机制仍有待确定。本文重点研究19-HB对非小细胞肺癌的抗肿瘤作用，为其进一步开发利用提供科学依据。研究了19-HB对人NSCLC细胞系NCI-H1299和NCI-H838的体外抗肿瘤作用。用不同浓度的19-HB处理细胞，通过CCK-8和集落形成实验检测细胞生长的抑制作用。流式细胞术、TUNEL染色、JC-1染色、western blotting检测细胞凋亡情况。通过创面愈合试验、transwell试验和免疫印迹法评估其对迁移和侵袭的影响。最后，利用异种移植小鼠模型评估19-HB的体内抗肿瘤作用。19- hb处理的NSCLC细胞表现出抑制细胞活力和增加凋亡的现象。cleaved- caspase-3、cleaved- parp、Bax/Bcl-2表达水平上调，线粒体膜电位降低。相反，迁移、侵袭以及MMP2、MMP7、MMP9、上皮间质转化相关蛋白N-cadherin和Vimentin以及转录因子Snail和Slug的表达均受到抑制。此外，Wnt/β-catenin信号通路关键分子CyclinD1、c-Myc和β-catenin的表达水平降低。在体内，19-HB也能显著抑制裸鼠异种移植肿瘤的生长，且肝肾功能生化指标无明显变化。19-HB通过Wnt/β-catenin通路抑制NSCLC细胞的增殖、迁移和侵袭，促进细胞凋亡。此外，19-HB还能抑制裸鼠异种移植瘤的生长，且对肝脏和肾脏的毒性很小。因此，19-HB可能是治疗非小细胞肺癌的潜在抗肿瘤药物。在线版本包含补充材料，可在10.1186/s40164-021-00243-0获得。
Bufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; however, its effects and underlying molecular mechanisms on tumor growth remain to be ascertained. In this report, we focused on the antitumor effects of 19-HB on non-small cell lung cancer to provide a scientific basis for its further development and utilization. The antitumor effects of 19-HB on the human NSCLC cell lines NCI-H1299 and NCI-H838 were examined in vitro. The cells were treated with different concentrations of 19-HB, and the inhibition of cell growth was measured by CCK-8 and colony formation assays. Furthermore, cell apoptosis was analyzed by flow cytometry, TUNEL staining, JC-1 staining, and western blotting. The effects on migration and invasion were evaluated by wound-healing assay, transwell assay, and western blotting. Finally, the antitumor effects of 19-HB were evaluated in vivo using a xenograft mouse model. 19-HB-treated NSCLC cells showed inhibited cell viability and increased apoptosis. The expression levels of cleaved caspase-3, cleaved-PARP, and Bax/Bcl-2 were upregulated, while the mitochondrial membrane potential decreased. In contrast, migration, invasion, as well as the expression of MMP2, MMP7, MMP9, the epithelial–mesenchymal transition-related proteins N-cadherin and Vimentin, and the transcription factors Snail and Slug were inhibited. Furthermore, the expression levels of the key molecules in the Wnt/β-catenin signaling pathway (CyclinD1, c-Myc, and β-catenin) were decreased. In vivo, the growth of xenograft tumors in nude mice was also significantly inhibited by 19-HB, and there were no significant changes in biochemical indicators of hepatic and renal function. 19-HB inhibited the proliferation, migration, and invasion, and promoted the apoptosis of NSCLC cells via the Wnt/β-catenin pathway. In addition, 19-HB inhibited the growth of xenograft tumors in nude mice with little toxicity to the liver and kidney. Thus, 19-HB may be a potential antitumor agent for treating NSCLC. The online version contains supplementary material available at 10.1186/s40164-021-00243-0.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
7.2
作者：
Feng Y;Chen Y;Meng Y;Cao Q;Liu Q;Ling C;Wang C
通讯作者：
Wang C
影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
6.2
作者：
Meng, Zhiqiang;Yang, Peiying;Shen, Yehua;Bei, Wenying;Zhang, Ying;Ge, Yongqian;Newman, Robert A.;Cohen, Lorenzo;Liu, Luming;Thornton, Bob;Chang, David Z.;Liao, Zongxing;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle
DOI：
10.1016/j.mrfmmm.2011.09.010
发表时间：
2012-04-01
影响因子：
2.3
作者：
Huang, Wen-Wen;Yang, Jai-Sing;Chung, Jing-Gung
通讯作者：
Chung, Jing-Gung