Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, PR China.
Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, PR China.
Life Sci. 2020 Sep 15;257:118100. doi: 10.1016/j.lfs.2020.118100. Epub 2020 Jul 14.
Nexrutine, an herbal extract of Phellodendron amurense, has been found to play a tumor-suppressive role in many cancers. However, its role in the pathogenesis of gastric cancer remains unclear.
Gastric cancer cells (SGC-7901 and MGC-803) were treated with nexrutine, and cell proliferation, invasion and apoptosis were analyzed. And the MGC-803 cells-derived xenograft mouse models were fed pelleted diet containing 600 mg/kg nexrutine for 21 days after inoculation. Mechanically, we focused on the influences of nexrutine on the levels and activation of STAT3 and NF-κB as well as their upstream regulator FAK. Additionally, we further verified whether nexrutine affected the proliferation, invasion and apoptosis of gastric cancer cells via FAK by upregulating FAK expression before nexrutine treatment.
We found nexrutine inhibited the viability, invasion, and expression levels of PCNA, CyclinD1 and Bcl-2, promoted the apoptosis and Bax expression, decreased levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, FAK and phospho-FAK in gastric cancer cells. Overexpression of FAK reversed the impacts of nexrutine on the levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, as well as the malignant characteristics of gastric cancer cells. Moreover, nexrutine suppressed tumor volumes and weights, and decreased expression and phosphorylation of FAK, STAT3 and NF-κB p65 in vivo.
Nexrutine inhibited the malignant progression of gastric cancer via negatively regulating STAT3/NF-κB signaling pathway by suppressing FAK expression and activation.
黄柏的一种草药提取物——黄柏碱，已被发现对许多癌症具有肿瘤抑制作用。然而，其在胃癌发病机制中的作用尚不清楚。
用黄柏碱处理胃癌细胞（SGC-7901 和 MGC-803），分析细胞增殖、侵袭和凋亡。接种后，用含 600mg/kg 黄柏碱的颗粒饲料喂养 MGC-803 细胞来源的异种移植小鼠模型 21 天。从机制上，我们主要关注黄柏碱对 STAT3 和 NF-κB 水平和激活及其上游调节因子 FAK 的影响。此外，我们通过在黄柏碱处理前上调 FAK 表达，进一步验证了黄柏碱是否通过 FAK 影响胃癌细胞的增殖、侵袭和凋亡。
我们发现黄柏碱抑制胃癌细胞的活力、侵袭和 PCNA、CyclinD1 和 Bcl-2 的表达水平，促进凋亡和 Bax 表达，降低胃癌细胞中 STAT3、磷酸化 STAT3、NF-κB p65、磷酸化 p65、FAK 和磷酸化 FAK 的水平。FAK 的过表达逆转了黄柏碱对 STAT3、磷酸化 STAT3、NF-κB p65、磷酸化 p65 以及胃癌细胞恶性特征的影响。此外，黄柏碱在体内抑制了肿瘤体积和重量，并降低了 FAK、STAT3 和 NF-κB p65 的表达和磷酸化。
黄柏碱通过抑制 FAK 的表达和激活，负调控 STAT3/NF-κB 信号通路，抑制胃癌的恶性进展。
