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菜蓟苦素通过LIFR/STATs轴的介导显示出对结直肠癌肿瘤进展的潜在抑制作用。

Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis.

作者信息

Zheng Dandan, Zhu Yu, Shen Yili, Xiao Sisi, Yang Lehe, Xiang Youqun, Dai Xuanxuan, Hu Wanle, Zhou Bin, Liu Zhiguo, Zhao Haiyang, Zhao Chengguang, Huang Xiaoying, Wang Liangxing

机构信息

The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

出版信息

Front Cell Dev Biol. 2021 Jan 11;8:605184. doi: 10.3389/fcell.2020.605184. eCollection 2020.

DOI:10.3389/fcell.2020.605184
PMID:33505963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7829511/
Abstract

BACKGROUND

Colorectal cancer (CRC) is the second deadliest malignant disease in the world and the leukemia inhibitory factor receptor/signal transducers and activators of transcriptions (LIFR/STATs) signaling axis plays an important role in the molecular biology of CRC.

METHODS

Cell function tests were performed to observe the inhibitory effect of cynaropicrin on human CRC cells (RKO, HCT116, and DLD-1). Expression levels of LIFR, P-STAT3, P-STAT4, and apoptotic proteins were detected by Western blotting. Immunoprecipitation confirmed the presence of LIFR/STAT3/STAT4 complex. Cell immunofluorescence assay was used to observe the subcellular localization of STAT3 and STAT4. efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice.

RESULTS

Cynaropicrin significantly reduced the survival ability of human CRC cells and promoted apoptosis in a dose-dependent manner. Western blotting results suggested that the antitumor effects of cynaropicrin might be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus. Cynaropicrin also suppressed tumor growth in the xenograft model.

CONCLUSION

The results showed that cynaropicrin exerted a strong inhibitory effect on CRC and . Our study concluded that cynaropicrin has potential application prospects in the field of anti-CRC therapy.

摘要

背景

结直肠癌（CRC）是全球第二大致命性恶性疾病，白血病抑制因子受体/信号转导和转录激活因子（LIFR/STATs）信号轴在CRC的分子生物学中起重要作用。

方法

进行细胞功能测试以观察洋蓟素对人CRC细胞（RKO、HCT116和DLD-1）的抑制作用。通过蛋白质免疫印迹法检测LIFR、P-STAT3、P-STAT4和凋亡蛋白的表达水平。免疫沉淀法证实了LIFR/STAT3/STAT4复合物的存在。采用细胞免疫荧光测定法观察STAT3和STAT4的亚细胞定位。通过裸鼠异种移植模型评估洋蓟素的疗效。

结果

洋蓟素显著降低人CRC细胞的存活能力，并以剂量依赖性方式促进细胞凋亡。蛋白质免疫印迹结果表明，洋蓟素的抗肿瘤作用可能是通过抑制LIFR/STATs轴介导的。洋蓟素减少了STAT3/STAT4异二聚体的形成，并阻止它们进入细胞核。洋蓟素还抑制了异种移植模型中的肿瘤生长。

结论

结果表明，洋蓟素对CRC具有强大的抑制作用。我们的研究得出结论，洋蓟素在抗CRC治疗领域具有潜在的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/168e02a1419e/fcell-08-605184-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/2a9363bf480b/fcell-08-605184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/5efbf703c796/fcell-08-605184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/7f062d980f91/fcell-08-605184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/18e810dfff6f/fcell-08-605184-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/0b721495ab76/fcell-08-605184-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/6a3e84337bf9/fcell-08-605184-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/168e02a1419e/fcell-08-605184-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/2a9363bf480b/fcell-08-605184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/5efbf703c796/fcell-08-605184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/7f062d980f91/fcell-08-605184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/18e810dfff6f/fcell-08-605184-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/0b721495ab76/fcell-08-605184-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/6a3e84337bf9/fcell-08-605184-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/7829511/168e02a1419e/fcell-08-605184-g007.jpg

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