肝细胞癌（HCC）对传统治疗方法提出了持续的挑战。 SLC12A5 具有致癌能力并促进癌症的进展。本研究的目的是检查硼砂对 HepG2 细胞中 SLC12A5 介导的内质网 (ER) 应激和细胞凋亡的抑制作用。最初，我们评估了硼砂对 HL-7702 和 HepG2 细胞系的细胞毒性影响。随后，检查了硼砂对这些细胞系的细胞形态和细胞周期的影响。随后，我们探讨了硼砂处理对 SLC12A5、C/EBP 同源蛋白 (CHOP)、葡萄糖调节蛋白 78 (GRP78)、激活转录因子 6 (ATF6)、caspase- mRNA 和蛋白表达水平的影响。这些细胞群中存在 3 (CASP3) 和细胞色素 c (CYC)。硼砂对于 HL-7702 细胞的测定 IC50 值为 40.8 mM，而对于 HepG2 细胞，该值为 22.6 mM。硼砂在HepG2细胞中的IC50浓度（22.6mM）和IC75浓度（45.7mM）在HL-7702细胞中没有表现出形态异常。相反，HepG2 细胞中的这些浓度会诱导可观察到的形态和细胞核异常，导致细胞周期停滞在 G1/G0 期。此外，与 HL-7702 细胞相比，HepG2 细胞中的 SLC12A5、ATF6、CHOP、GRP78、CASP3 和 CYC 水平升高。此外，HepG2细胞中硼砂处理后SLC12A5水平下降，而ATF6、CHOP、GRP78、CASP3和CYC水平显着增加。总之，我们的数据强调了硼砂通过靶向 SLC12A5 来调节 HCC ER 应激的潜在治疗效果。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

Hepatocellular carcinoma (HCC) presents a persistent challenge to conventional therapeutic approaches. SLC12A5 is implicated in an oncogenic capacity and facilitates the progression of cancer. The objective of this investigation is to scrutinize the inhibitory effects of borax on endoplasmic reticulum (ER)-stress and apoptosis mediated by SLC12A5 in HepG2 cells. Initially, we evaluated the cytotoxic impact of borax on both HL-7702 and HepG2 cell lines. Subsequently, the effects of borax on cellular morphology and the cell cycle of these lines were examined. Following this, we explored the impact of borax treatment on the mRNA and protein expression levels of SLC12A5, C/EBP homologous protein (CHOP), glucose-regulated protein-78 (GRP78), activating transcription factor-6 (ATF6), caspase-3 (CASP3), and cytochrome c (CYC) in these cellular populations. The determined IC50 value of borax for HL-7702 cells was 40.8 mM, whereas for HepG2 cells, this value was 22.6 mM. The concentrations of IC50 (22.6 mM) and IC75 (45.7 mM) of borax in HepG2 cells did not manifest morphological aberrations in HL-7702 cells. Conversely, these concentrations in HepG2 cells induced observable morphological and nuclear abnormalities, resulting in cell cycle arrest in the G1/G0 phase. Additionally, the levels of SLC12A5, ATF6, CHOP, GRP78, CASP3, and CYC were elevated in HepG2 cells in comparison to HL-7702 cells. Moreover, SLC12A5 levels decreased following borax treatment in HepG2 cells, whereas ATF6, CHOP, GRP78, CASP3, and CYC levels exhibited a significant increase. In conclusion, our data highlight the potential therapeutic effects of borax through the regulation of ER stress in HCC by targeting SLC12A5.© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.