Li Lanyu, Yang Lukai, Liu Fang, Qu Jinfeng
Department of Obstetrics and Gynecology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, China.
Department of Gastroenterology & GI Endoscopy Center, Dongying People's Hospital, Dongying 257091, China.
Evid Based Complement Alternat Med. 2022 Jun 13;2022:8330926. doi: 10.1155/2022/8330926. eCollection 2022.
Endometrial cancer (EC) is a common malignant tumor of the female reproductive system. Current treatments such as surgery and long-term hormone therapy are ineffective and have side effects. Danzhi Xiaoyao powder (DXP) can inhibit the growth of EC cells and induce apoptosis, but the pharmacological and molecular mechanisms of anticancer effects are still unclear. In this study, active components and potential targets of DXP were obtained from public databases. Protein effects and regulatory pathways of common targets were analyzed by protein-protein interaction (PPI), GO and KEGG. The results of network pharmacology showed that there are 87 common targets between EC and DXP. GO enrichment analysis showed that these targets were associated with response to oxidative stress, response to nutrient levels, hormone receptor binding and nuclear hormone receptor binding, etc. The results of KEGG analysis indicated that IL-17, TNF, PI3K/AKT, and RAS/RAF/MEK/ERK (ERK) signaling pathway were enriched in the anti-EC of DXP. Additionally, we cultured HEC-1B and KLE cells for validate experiments. DXP showed an inhibition of proliferation, migration, and cell cycle of both cells. Moreover, the expression of RAS, p-RAF, p-MEK, ERK, and p-ERK related proteins were downregulated. In conclusion, DXP might inhibit the proliferation of EC cells via apoptosis. Furthermore, DXP-induced inhibition of EC development might involve RAS/RAF/MEK/ERK pathway.
子宫内膜癌(EC)是女性生殖系统常见的恶性肿瘤。目前的治疗方法,如手术和长期激素治疗,效果不佳且有副作用。丹栀逍遥散(DXP)可抑制EC细胞生长并诱导其凋亡,但其抗癌作用的药理和分子机制仍不清楚。本研究从公共数据库中获取DXP的活性成分和潜在靶点。通过蛋白质-蛋白质相互作用(PPI)、基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析共同靶点的蛋白质作用和调控途径。网络药理学结果显示,EC与DXP之间有87个共同靶点。GO富集分析表明,这些靶点与氧化应激反应、营养水平反应、激素受体结合和核激素受体结合等有关。KEGG分析结果表明,白细胞介素-17(IL-17)、肿瘤坏死因子(TNF)、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)和RAS/RAF/丝裂原活化蛋白激酶/细胞外信号调节激酶(RAS/RAF/MEK/ERK,ERK)信号通路在DXP抗EC作用中富集。此外,我们培养人子宫内膜癌细胞系HEC-1B和KLE细胞进行验证实验。DXP对两种细胞的增殖、迁移和细胞周期均有抑制作用。此外,RAS、磷酸化RAF(p-RAF)、磷酸化MEK(p-MEK)、ERK和磷酸化ERK(p-ERK)相关蛋白的表达下调。综上所述,DXP可能通过诱导凋亡抑制EC细胞增殖。此外,DXP诱导的EC发展抑制可能涉及RAS/RAF/MEK/ERK信号通路。