Guo Yusheng, Cai Xiangsheng, Lu Hanwei, Li Qiqi, Zheng Ying, Lin Zefang, Cheng Zexiong, Yang Maoxiang, Zhang Li, Xiang Lei, Yang Xiaorong
Clinical Laboratory, First Affiliated Hospital/School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Department of Medical Laboratory, School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Front Pharmacol. 2021 Mar 15;12:607379. doi: 10.3389/fphar.2021.607379. eCollection 2021.
Liver cancer is associated with high mortality, particularly in patients infected with the hepatitis B virus. Treatment methods remain very limited. Here, we explored the effects of 17β-estradiol (E2) on apoptosis of various liver cell lines (LO2, HepG2, and HepG2.2.15 cells). Within a certain concentration range, 17β-estradiol induced oxidative stress and apoptosis of HepG2 cells, downregulated ERα-36 expression, and increased Akt and Foxo3a phosphorylation. -Foxo3a became localized around the nucleus but did not enter the organelle. The levels of mRNAs encoding manganese superoxide dismutase (MnSOD) and catalase, to the promoters of which Foxo3a binds to trigger gene expression, were significantly reduced in HepG2 cells. 17β-estradiol had no obvious effects on LO2 or HepG2.2.15 cells. We speculate that 17β-estradiol may induce oxidative stress in HepG2 cells by increasing Foxo3a phosphorylation, thus promoting apoptosis. This may serve as a new treatment for hepatocellular carcinoma.
肝癌与高死亡率相关，尤其是在感染乙肝病毒的患者中。治疗方法仍然非常有限。在此，我们探究了17β-雌二醇（E2）对各种肝细胞系（LO2、HepG2和HepG2.2.15细胞）凋亡的影响。在一定浓度范围内，17β-雌二醇诱导HepG2细胞发生氧化应激和凋亡，下调ERα-36表达，并增加Akt和Foxo3a磷酸化。Foxo3a定位于细胞核周围，但未进入细胞器。在HepG2细胞中，编码锰超氧化物歧化酶（MnSOD）和过氧化氢酶的mRNA水平显著降低，而Foxo3a会与这些酶的启动子结合以触发基因表达。17β-雌二醇对LO2或HepG2.2.15细胞没有明显影响。我们推测，17β-雌二醇可能通过增加Foxo3a磷酸化来诱导HepG2细胞发生氧化应激，从而促进凋亡。这可能成为肝细胞癌的一种新的治疗方法。
