Department of Gastroenterology, Shanxian Dongda Hospital.
Department of General Surgery, Shanxian Dongda Hospital.
Biol Pharm Bull. 2021;44(6):780-788. doi: 10.1248/bpb.b20-00822.
Gastric cancer is one of the most common malignancies with a high mortality rate world. This study intends to make clear the role and mechanism of the Scutellarin (Scu), a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz, in regulating the evolvement of gastric cancer. We selected different doses of Scu to treat gastric cancer cells (MGC-803 and AGS). Then, cell counting kit-8 (CCK8) assay was conducted to verify the proliferation of tumor cells, while flow cytometry was adopted to test the apoptosis rate. Meanwhile, Western blot was conducted to examine epithelial-mesenchymal transition (EMT) markers and the expression of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K) and apoptosis-related proteins (Bax, Bcl2 and Caspase3). Moreover, xenograft tumor experiment in nude mice was established to verify the effect of Scu on tumor growth. Furthermore, the knockdown model of PTEN was constructed, and the influence of PTEN on the anti-tumor effect of Scu was investigated. As a result, Scu inhibited cell proliferation, EMT and promoted the apoptosis in gastric cancer dose-dependently. Additionally, Scu attenuated tumor cell growth in vivo. Besides, Scu enhanced the expression of PTEN while reduced the phosphorylated level of PI3K. Moreover, the mechanistic study proved that Scu inactivated PI3K by up-regulating PTEN, thus dampening tumor progression. In conclusion, Scu dampened the growth and EMT of gastric cancer by regulating the PTEN/PI3K pathway.
胃癌是全球死亡率较高的最常见恶性肿瘤之一。本研究旨在阐明从灯盏花中分离得到的黄酮类化合物野黄芩苷（Scu）在调控胃癌演变中的作用和机制。我们选择了不同剂量的 Scu 来治疗胃癌细胞（MGC-803 和 AGS）。然后，通过细胞计数试剂盒-8（CCK8）检测来验证肿瘤细胞的增殖情况，而采用流式细胞术检测细胞凋亡率。同时，通过 Western blot 检测上皮间质转化（EMT）标志物以及磷酸酶和张力蛋白同源物（PTEN）/磷脂酰肌醇 3-激酶（PI3K）和凋亡相关蛋白（Bax、Bcl2 和 Caspase3）的表达。此外，还建立了裸鼠异种移植肿瘤实验来验证 Scu 对肿瘤生长的影响。进一步构建了 PTEN 的敲低模型，研究了 PTEN 对 Scu 抗肿瘤作用的影响。结果表明，Scu 呈剂量依赖性地抑制胃癌细胞的增殖、EMT 并促进细胞凋亡。此外，Scu 还能在体内减弱肿瘤细胞的生长。此外，Scu 增强了 PTEN 的表达，同时降低了 PI3K 的磷酸化水平。此外，机制研究证明 Scu 通过上调 PTEN 使 PI3K 失活，从而抑制肿瘤进展。综上所述，Scu 通过调节 PTEN/PI3K 通路来抑制胃癌的生长和 EMT。
