Department of Oncology, Guang'anmen Hospital South Campus, China Academy of Chinese Medical Sciences, Beijing, China.
Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
J Physiol Pharmacol. 2023 Oct;74(5). doi: 10.26402/jpp.2023.5.10. Epub 2023 Dec 6.
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.
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）。最近发现醇脱氢酶 1B（ADH1B）与 BRCA 患者的预后不良有关。本研究确定了 ADH1B 对 BRCA 和 TNBC 进展的确切作用。基于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 和体内测定研究了 ADH1B 对 BRCA 和 TNBC 细胞增殖、侵袭和迁移以及生长的影响。Western blot 用于确定 ADH1B 对丝裂原活化蛋白激酶（MAPK）信号通路活性的影响。结果显示，ADH1B 在 BRCA 和 TNBC 患者和细胞中下调，预示着不良预后（P<0.05）。ADH1B 过表达抑制 BRCA 和 TNBC 细胞的增殖、侵袭和迁移，并使 MAPK 信号通路失活（P<0.01）。ADH1B 与 Selumetinib（MAPK 信号通路抑制剂）协同作用，减弱 BRCA 和 TNBC 细胞的增殖、侵袭和迁移（P<0.001）。相反，Vacquinol-1（MAPK 信号通路激活剂）消除了 ADH1B 对 BRCA 和 TNBC 细胞增殖、侵袭和迁移的抑制作用（P<0.05）。ADH1B 抑制 TNBC 细胞的体内生长（P<0.001）。因此，ADH1B 可能通过使 MAPK 信号通路失活来抑制 BRCA 和 TNBC 细胞的增殖、侵袭和迁移。它可能成为 BRCA 和 TNBC 临床治疗的有前途的靶点。
