College of Health & Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Int J Mol Sci. 2020 Oct 16;21(20):7664. doi: 10.3390/ijms21207664.
ABCC1 and ABCC4 utilize energy from ATP hydrolysis to transport many different molecules, including drugs, out of the cell and, as such, have been implicated in causing drug resistance. However recently, because of their ability to transport signaling molecules and inflammatory mediators, it has been proposed that ABCC1 and ABCC4 may play a role in the hallmarks of cancer development and progression, independent of their drug efflux capabilities. Breast cancer is the most common cancer affecting women. In this study, the aim was to investigate whether ABCC1 or ABCC4 play a role in the proliferation or migration of breast cancer cell lines MCF-7 (luminal-type, receptor-positive) and MDA-MB-231 (basal-type, triple-negative). The effects of small molecule inhibitors or siRNA-mediated knockdown of ABCC1 or ABCCC4 were measured. Colony formation assays were used to assess the clonogenic capacity, MTT assays to measure the proliferation, and scratch assays and Transwell assays to monitor the cellular migration. The results showed a role for ABCC1 in cellular proliferation, whilst ABCC4 appeared to be more important for cellular migration. ELISA studies implicated cAMP and/or sphingosine-1-phosphate efflux in the mechanism by which these transporters mediate their effects. However, this needs to be investigated further, as it is key to understand the mechanisms before they can be considered as targets for treatment.
ABCC1 和 ABCC4 利用 ATP 水解产生的能量将许多不同的分子，包括药物，从细胞内排出，因此它们与药物耐药性的产生有关。然而，最近由于它们能够转运信号分子和炎症介质，有人提出 ABCC1 和 ABCC4 可能在癌症发展和进展的标志性特征中发挥作用，而与它们的药物外排能力无关。乳腺癌是最常见的女性癌症。在这项研究中，目的是研究 ABCC1 或 ABCC4 是否在乳腺癌细胞系 MCF-7（腔型，受体阳性）和 MDA-MB-231（基底型，三阴性）的增殖或迁移中发挥作用。测量了小分子抑制剂或 siRNA 介导的 ABCC1 或 ABCCC4 敲低的效果。集落形成实验用于评估集落形成能力，MTT 实验用于测量增殖，划痕实验和 Transwell 实验用于监测细胞迁移。结果表明 ABCC1 在细胞增殖中起作用，而 ABCC4 似乎对细胞迁移更为重要。ELISA 研究表明，cAMP 和/或 1-磷酸鞘氨醇的外排在这些转运蛋白介导其作用的机制中起作用。然而，这需要进一步研究，因为在考虑将其作为治疗靶点之前，了解这些机制是关键。
