Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Arch Physiol Biochem. 2022 Oct;128(5):1150-1155. doi: 10.1080/13813455.2020.1760304. Epub 2020 May 14.
YAP and TAZ, two closely related transcriptional regulators, have crucial roles in tissue repair upon injury, organ size control, and cancer treatment. Some drugs, such as metformin, that alter cell metabolism can play a role in the regulation of the Hippo pathway. The cells were treated with various concentrations of metformin, dacarbazine (IC), and both of them. The evaluation of the biomarker and proteins was performed by FACS and immunoblotting, respectively. Cell viability was reduced by 50% after 24 h. Data showed that metformin treatment down-regulated YAP and TAZ ( = .002) expressions and enhanced YAP phosphorylation ( < .001). Metformin, alone and in combination, inhibited the growth and viability of melanoma cells . The increase in the phosphorylation of YAP renders it a potential target in the development of anticancer drugs. This study showed the effects of metformin on the inhibition of oncogenic YAP and TAZ in the proliferation of melanoma cells.
YAP 和 TAZ 是两个密切相关的转录调节因子，在损伤后的组织修复、器官大小控制和癌症治疗中起着关键作用。一些改变细胞代谢的药物，如二甲双胍，可以在 Hippo 通路的调节中发挥作用。用不同浓度的二甲双胍、达卡巴嗪（IC）和它们的组合处理细胞。通过 FACS 和免疫印迹分别评估生物标志物和蛋白质。24 小时后，细胞活力降低了 50%。数据表明，二甲双胍治疗下调 YAP 和 TAZ（= 0.002）的表达，并增强 YAP 的磷酸化（< 0.001）。二甲双胍单独和联合使用均可抑制黑色素瘤细胞的生长和活力。YAP 磷酸化的增加使其成为开发抗癌药物的潜在靶点。本研究表明，二甲双胍对抑制黑色素瘤细胞增殖中的致癌 YAP 和 TAZ 的作用。
