Yuan Chenchen, Wu Chenchen, Xue Rong, Jin Chun, Zheng Chenguo
Department of Coloproctology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109 Xueyuan Western Road, Wenzhou, Zhejiang Province, 325000, P.R. China.
J Cancer. 2021 Aug 8;12(19):5914-5922. doi: 10.7150/jca.61581. eCollection 2021.
Ethanol extracted from radix of Actinidia chinensis (EERAC) has been proved to be effective to inhibit colorectal cancer (CRC). Notch signaling pathway and angiogenesis in tumors are closely related with the progression of CRC. However, if EERAC could influence CRC through Notch signaling pathway and angiogenesis remains unclear. Flow cytometry, transwell, wound healing methods were used to measure cell apoptosis, invasion, migration, and proliferation. Protein and mRNA expression were detected using qRT-PCR and western blotting. Immunofluorescence staining was applied to detect the expression of target protein in the tissues. The invasion, migration, and proliferation of CRC cells were remarkably suppressed by ERRAC. Significant promotion of cell apoptosis and cell ration in S stage were observed after EERAC treatment. The Notch1/DLL4/Hes1 signaling pathway and angiogenesis were suppressed by EERAC. Overexpression of LIM domain-binding 2 (LDB2) remarkably weakened the influence of ERRAC on the viability of CRC cells. EERAC might suppress CRC through targeting Notch/DLL4/Hes1 pathway and inhibiting angiogenesis in tumors. This study might provide novel thought for the prevention and therapy of CRC through targeting Notch/DLL4/Hes1.
中华猕猴桃根提取物乙醇提取物(EERAC)已被证明对抑制结直肠癌(CRC)有效。肿瘤中的Notch信号通路和血管生成与CRC的进展密切相关。然而,EERAC是否能通过Notch信号通路和血管生成影响CRC仍不清楚。采用流式细胞术、Transwell、伤口愈合方法检测细胞凋亡、侵袭、迁移和增殖。使用qRT-PCR和western blotting检测蛋白质和mRNA表达。应用免疫荧光染色检测组织中靶蛋白的表达。ERRAC显著抑制了CRC细胞的侵袭、迁移和增殖。EERAC处理后观察到细胞凋亡和S期细胞比例显著增加。EERAC抑制了Notch1/DLL4/Hes1信号通路和血管生成。LIM结构域结合2(LDB2)的过表达显著减弱了ERRAC对CRC细胞活力的影响。EERAC可能通过靶向Notch/DLL4/Hes1通路并抑制肿瘤血管生成来抑制CRC。本研究可能为通过靶向Notch/DLL4/Hes1预防和治疗CRC提供新的思路。