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氟噻唑基腙类化合物 TSC-3C 通过促进细胞凋亡、调节 MAPK 通路和诱导线粒体功能障碍来抑制三阴性乳腺癌(TNBC)细胞系的活性。

The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by Promoting Apoptosis, Regulating the MAPK Pathway and Inducing Mitochondrial Dysfunction.

机构信息

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.

Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China.

出版信息

Int J Mol Sci. 2020 Feb 4;21(3):1038. doi: 10.3390/ijms21031038.

Abstract

Triple negative breast cancer (TNBC) is the most aggressive cancer in women, and despite improved treatments, it remains a major cause of morbidity and mortality. We and others have demonstrated that different hybrid compounds targeting PARP/MAPK or other pathways to inhibit cancer progression may lead to promising therapeutic results. We introduced fluorine to alter the physical properties of the compounds. TSC-3C was one of the generated compounds. Upon treatment with TSC-3C, MDA-MB-231 cell proliferation, invasion, and migration were inhibited. induced MDA-MB-231 cell mitochondrial dysfunction and apoptosis, which may be caused by reducing the level of phosphorylated p44/42 MAPK (ERK1/2) and increasing the level of p-JNK. The present study may help to elucidate the role of the MAPK pathway in the development of breast cancer and may promote further research on halogenated heterocyclic compounds for the treatment of breast cancer.

摘要

三阴性乳腺癌(TNBC)是女性中最具侵袭性的癌症,尽管治疗有所改善,但仍是发病率和死亡率的主要原因。我们和其他人已经证明,针对 PARP/MAPK 或其他通路的不同杂交化合物来抑制癌症进展可能会带来有前景的治疗结果。我们引入氟来改变化合物的物理性质。TSC-3C 是生成的化合物之一。用 TSC-3C 处理后,抑制了 MDA-MB-231 细胞的增殖、侵袭和迁移。TSC-3C 诱导 MDA-MB-231 细胞线粒体功能障碍和细胞凋亡,这可能是由于降低了磷酸化 p44/42 MAPK(ERK1/2)的水平和增加了 p-JNK 的水平。本研究可能有助于阐明 MAPK 通路在乳腺癌发展中的作用,并可能促进进一步研究用于治疗乳腺癌的卤代杂环化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef91/7038075/cb70280abcea/ijms-21-01038-sch001.jpg

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