Zhao Jing, Shi Yunfu, Ma Yubo, Pan Libin, Wang Yanan, Yuan Li, Dong Jinyun, Ying Jieer
Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Front Pharmacol. 2023 Mar 1;14:1143427. doi: 10.3389/fphar.2023.1143427. eCollection 2023.
Gastric cancer (GC) is a prevalent malignant neoplasm that poses a serious threat to human health. Overexpression of Aurora A (AURKA) is frequently associated with the self-renewal and tumorigenicity of various cancers. Chebulagic acid (CA) has been examined as a potential tumor suppressor based on its ability against numerous tumor biological activities. However, the possible mechanisms of CA inhibition of the progression of GC by mediating the AURKA/β-catenin/Wnt signaling pathway have not been investigated. The present study investigated the level of AURKA expression in GC. We further examined the effect of CA on cell proliferation, migration, and apoptosis in the MKN1 and NUGC3 GC cell lines, and its efficacy in suppressing tumor growth was assessed in tumor bearing mice model. We demonstrated that AURKA was highly expressed in GC and associated with poor prognosis. We demonstrated that treatment with CA significantly inhibited the proliferation and migration of GC cells and induced apoptosis. Compared to the vehicle group, CA treatment severely diminished the volume and weight and the metastasis of tumors. CA also inhibited the expression of AURKA and the AURKA/β-catenin/Wnt signaling pathway and . Collectively, the present results demonstrated that high expression of AURKA may be an independent factor of poor prognosis in patients with GC, and CA significantly suppressed the tumor biological functions of GC and inhibited the AURKA/β-catenin/Wnt pathway.
胃癌(GC)是一种常见的恶性肿瘤,对人类健康构成严重威胁。极光激酶A(AURKA)的过表达常与多种癌症的自我更新和致瘤性相关。基于诃子酸(CA)对多种肿瘤生物学活性的抑制能力,其已被作为一种潜在的肿瘤抑制因子进行研究。然而,CA通过介导AURKA/β-连环蛋白/Wnt信号通路抑制GC进展的可能机制尚未得到研究。本研究调查了GC中AURKA的表达水平。我们进一步检测了CA对MKN1和NUGC3 GC细胞系中细胞增殖、迁移和凋亡的影响,并在荷瘤小鼠模型中评估了其抑制肿瘤生长的功效。我们证明AURKA在GC中高表达且与预后不良相关。我们证明CA处理显著抑制了GC细胞的增殖和迁移并诱导了凋亡。与载体组相比,CA处理显著减小了肿瘤的体积、重量及转移。CA还抑制了AURKA的表达以及AURKA/β-连环蛋白/Wnt信号通路。总体而言,本研究结果表明AURKA的高表达可能是GC患者预后不良的一个独立因素,且CA显著抑制了GC的肿瘤生物学功能并抑制了AURKA/β-连环蛋白/Wnt通路。