Hu Wanle, Wu Chenchen, Yuan Chenchen, Chen Minyuan, 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, 325027, P.R. China.
J Cancer. 2021 Jan 1;12(3):622-629. doi: 10.7150/jca.51275. eCollection 2021.
Colorectal cancer (CRC) is one of the most common tumors, and its five-year survival is still very low despite of the advance of treatment strategies. The antitumor effect of ethanol extracted from radix of Actinidia chinensis (EERAC) were identified in human colon cancer cells, but the underlying mechanism remains unclear. Cell proliferation, migration, and invasion were measured with cell counting kit-8 (CCK-8), wound healing, and transwell assays. Cell apoptosis and cycle were detected by flow cytometry. Western blotting and qRT-PCR were used to measure expression of target molecules. Xenograft tumor assay was applied to detect the influence of EERAC on tumor growth. we found that EERAC inhibited the cell viability, migration, and invasion of SW480 cells in a concentration dependent manner, but promoted apoptosis and the cell percentage in S phase significantly. The suppression of notch-signaling pathway molecules, Notch1, Jagged1, and c-Myc, by EERAC was confirmed using western blotting and immunohistochemical staining. The significant inhibition of tumor growth by EERAC was also observed. Meanwhile, EERAC remarkably reversed the effects of mastermind like transcriptional coactivator 1 (MAML1, activator of notch-signaling pathway) on cell survival of SW480. EERAC might be a promising chemotherapeutic agent for CRC treatment.
结直肠癌(CRC)是最常见的肿瘤之一,尽管治疗策略有所进步,但其五年生存率仍然很低。中华猕猴桃根乙醇提取物(EERAC)在人结肠癌细胞中具有抗肿瘤作用,但其潜在机制尚不清楚。采用细胞计数试剂盒-8(CCK-8)、伤口愈合试验和Transwell试验检测细胞增殖、迁移和侵袭能力。通过流式细胞术检测细胞凋亡和细胞周期。采用蛋白质免疫印迹法(Western blotting)和实时定量聚合酶链反应(qRT-PCR)检测靶分子的表达。应用异种移植瘤试验检测EERAC对肿瘤生长的影响。我们发现,EERAC以浓度依赖性方式抑制SW480细胞的活力、迁移和侵袭,但显著促进细胞凋亡和S期细胞百分比。通过蛋白质免疫印迹法和免疫组织化学染色证实EERAC对Notch信号通路分子Notch1、Jagged1和c-Myc有抑制作用。同时也观察到EERAC对肿瘤生长有显著抑制作用。此外,EERAC显著逆转了主调控因子样转录共激活因子1(MAML1,Notch信号通路激活剂)对SW480细胞存活的影响。EERAC可能是一种有前途的用于结直肠癌治疗的化疗药物。