酒精脱氢酶-1B通过使丝裂原活化蛋白激酶信号通路失活,抑制乳腺癌细胞的增殖、侵袭和迁移。

IF 2 4区 医学 Q3 PHYSIOLOGY Journal of Physiology and Pharmacology Pub Date : 2023-10-01 Epub Date: 2023-12-06 DOI:10.26402/jpp.2023.5.10
C Jiang, R Liu, X Wu
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引用次数: 0

摘要

乳腺癌(BRCA)是一种严重威胁生命的癌症,尤其是三阴性乳腺癌(TNBC)。最近发现,酒精脱氢酶-1B(ADH1B)与 BRCA 患者的不良预后有关。这项研究确定了ADH1B对BRCA和TNBC进展的确切功能。根据在线数据库和临床样本研究了ADH1B对BRCA和TNBC患者预后的影响。通过细胞计数试剂盒-8、Transwell和体内试验研究了ADH1B对BRCA和TNBC细胞增殖、侵袭、迁移和生长的作用。利用 Western 印迹测定了 ADH1B 对丝裂原活化蛋白激酶(MAPK)信号通路活性的影响。结果发现,ADH1B在BRCA和TNBC患者及细胞中下调,预示着预后不良(P<0.05)。
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Alcohol dehydrogenase-1B represses the proliferation, invasion and migration of breast cancer cells by inactivating the mitogen-activated protein kinase signalling pathway.

Breast cancer (BRCA) is a serious life-threatening cancer, especially triple-negative breast cancer (TNBC). Alcohol dehydrogenase-1B (ADH1B) has recently been revealed to be associated with poor prognosis of BRCA patients. This study identified the exact function of ADH1B on the progression of BRCA and TNBC. ADH1B effect on the prognosis of BRCA and TNBC patients was researched based on online databases and clinical samples. The function of ADH1B on the proliferation, invasion and migration, and growth of BRCA and TNBC cells was investigated by cell counting kit-8, Transwell, and in vivo assays. Western blot was utilized to determine the effect of ADH1B on the mitogen-activated protein kinase (MAPK) signalling pathway activity. As a result, ADH1B was down-regulated in BRCA and TNBC patients and cells, predicting unfavorable prognosis (P<0.05). ADH1B overexpression suppressed the proliferation, invasion and migration, and inactivated the MAPK signalling pathway in BRCA and TNBC cells (P<0.01). ADH1B synergized with Selumetinib (inhibitor of the MAPK signalling pathway) to attenuate the proliferation, invasion and migration of BRCA and TNBC cells (P<0.001). Conversely, Vacquinol-1 (activator of the MAPK signalling pathway) abolished the suppression of ADH1B on the proliferation, invasion and migration of BRCA and TNBC cells (P<0.05). ADH1B suppressed in vivo growth of TNBC cells (P<0.001). Thus, ADH1B may inhibit the proliferation, invasion and migration of BRCA and TNBC cells by inactivating the MAPK signalling pathway. It may be a promising target for the clinical treatment of BRCA and TNBC.

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CiteScore
4.00
自引率
22.70%
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6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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