Jin Mingji, Li Chunyu, Zhang Qiang, Xing Shu, Kan Xuan, Wang Jiayu
Department of Pharmacy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Otolaryngology, Daqing Longnan Hospital, Daqing, Heilongjiang 163453, P.R. China.
Oncol Lett. 2018 Jun;15(6):8454-8460. doi: 10.3892/ol.2018.8377. Epub 2018 Mar 29.
Aspirin may exhibit antitumor activities, as it is able to inhibit cell proliferation. However, the ability of aspirin to inhibit cellular proliferation in Hep-2 cells and its underlying molecular mechanisms have been poorly determined. The aim of the present study was to investigate whether aspirin may induce cell apoptosis in the neoplastic cell line Hep-2. The effects of aspirin on the migratory and invasive abilities of Hep-2 cells were also investigated using Transwell assays. In the present study, it was demonstrated that aspirin induced apoptosis and inhibited proliferation, migration and invasion in Hep-2 cells. Aspirin also significantly decreased the expression of B-cell lymphoma 2 (Bcl-2) and caspase-3, and increased the expression of Bcl-2-associated X protein, suggesting that aspirin induced apoptosis through the intrinsic apoptotic pathway. Hep-2 cells treated with aspirin exhibited a significant upregulation of phosphatase and tensin homolog (PTEN) and decreased levels of phosphorylated protein kinase B (AKT). However, the total amount of AKT protein was not altered in response to aspirin treatment. Furthermore, the expression of nuclear factor (NF)-κB and survivin, which are the downstream targets of the PTEN/AKT signaling pathway, was inhibited. These results indicated that the molecular mechanism underlying the antitumor effects of aspirin may be associated with the inhibition of tumor invasion and induction of apoptosis by regulating the activity of the PTEN/AKT/NF-κB/survivin signaling pathway.
阿司匹林可能具有抗肿瘤活性，因为它能够抑制细胞增殖。然而，阿司匹林抑制Hep-2细胞增殖的能力及其潜在的分子机制尚未得到充分确定。本研究的目的是探讨阿司匹林是否可诱导肿瘤细胞系Hep-2发生细胞凋亡。还使用Transwell实验研究了阿司匹林对Hep-2细胞迁移和侵袭能力的影响。在本研究中，已证明阿司匹林可诱导Hep-2细胞凋亡并抑制其增殖、迁移和侵袭。阿司匹林还显著降低了B细胞淋巴瘤2（Bcl-2）和半胱天冬酶-3的表达，并增加了Bcl-2相关X蛋白的表达，表明阿司匹林通过内在凋亡途径诱导细胞凋亡。用阿司匹林处理的Hep-2细胞表现出磷酸酶和张力蛋白同源物（PTEN）的显著上调以及磷酸化蛋白激酶B（AKT）水平的降低。然而，AKT蛋白的总量在阿司匹林处理后并未改变。此外，PTEN/AKT信号通路的下游靶点核因子（NF）-κB和生存素的表达受到抑制。这些结果表明，阿司匹林抗肿瘤作用的分子机制可能与通过调节PTEN/AKT/NF-κB/生存素信号通路的活性来抑制肿瘤侵袭和诱导细胞凋亡有关。
