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18β-甘草次酸通过抑制细胞增殖和迁移发挥强大的抗肿瘤作用对抗结直肠癌。

18 β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer via inhibition of cell proliferation and migration.

机构信息

Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.

Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Cancer Institute, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.

出版信息

Int J Oncol. 2017 Aug;51(2):615-624. doi: 10.3892/ijo.2017.4059. Epub 2017 Jun 27.

Abstract

Accumulating evidence shows that 18 β-glycyr-rhetinic acid (GRA) has antitumor activities in breast, ovarian cancer and leukemia, while its role in colorectal cancer remains unknown. In the present study, we investigated the effect of GRA in colorectal cancer cells LoVo, SW480 and SW620 and studied the underlying molecular mechanisms. Results showed that GRA had potent inhibitory effects on colorectal cancer cell proliferation in a dose- and time-dependent manner in vitro and in vivo. Growth inhibition was mediated by pro-apoptosis, as evident from Annexin V-FITC staining, the reduced expression of survivin and the induced expression of cleaved PARP. Furthermore, GRA treatment resulted in marked reduction of cell migration, invasion and wound healing capability, accompanying by the downregulated MMP expression. Moreover, GRA decreased the protein levels of p-PI3K, p-AKT, p-STAT3, p-JNK, p-p38 and p-NF-κB p65, of which the phosphorylation of PI3K and STAT3 decreased as early as 2 h after the GRA treatment. These results suggest that regulation of the apoptosis, invasion and migration of colorectal cancer cells by GRA might be through suppressing PI3K and STAT3 signaling pathways. the present study indicated that GRA could be a potential effective therapy for patients with colorectal cancer.

摘要

越来越多的证据表明,18β-甘草次酸(GRA)在乳腺癌、卵巢癌和白血病中具有抗肿瘤活性,但其在结直肠癌中的作用尚不清楚。在本研究中,我们研究了 GRA 对结直肠癌细胞 LoVo、SW480 和 SW620 的作用,并研究了其潜在的分子机制。结果表明,GRA 在体外和体内均以剂量和时间依赖的方式对结直肠癌细胞增殖具有很强的抑制作用。生长抑制是由促凋亡介导的,从 Annexin V-FITC 染色、survivin 表达降低和 cleaved PARP 的诱导表达可以明显看出。此外,GRA 处理导致细胞迁移、侵袭和伤口愈合能力显著降低,同时 MMP 表达下调。此外,GRA 降低了 p-PI3K、p-AKT、p-STAT3、p-JNK、p-p38 和 p-NF-κB p65 的蛋白水平,其中 PI3K 和 STAT3 的磷酸化早在 GRA 处理后 2 小时就降低了。这些结果表明,GRA 通过抑制 PI3K 和 STAT3 信号通路调节结直肠癌细胞的凋亡、侵袭和迁移。本研究表明,GRA 可能是结直肠癌患者的一种潜在有效治疗方法。

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