Given studies have shown that Artemisinin (ART) reduces cancer cell proliferation, migration, invasion, tumorigenesis and metastasis. In this study, we evaluated the roles of ART in clear cell renal cell carcinoma (ccRCC) progression. We measured the eff ;ects of ART on cancer cell proliferation, colony formation, migration, invasion and tumorigenesis. CCK-8 assay demonstrated that ART inhibited cell growth with IC50 values 31.30 ± 0.73 μM in UMRC-2 and 23.97 ± 0.92 μM in CAKI-2, respectively. Colony formation assay shown that ART inhibited cell colony formation. Transwell migration and invasion assay shown that ART inhibited RCC migration and invasion. Realtime-qPCR assay shown that ART decreased the mRNA levels of proliferation related genes c-Myc, cyclin D1 and PCNA, and reduced the mRNA levels of mesenchymal genes N-cadherin, Vimentin and Snail, but increased the mRNA levels of epithelial marker E-cadherin. Moreover, ART inhibited AKT signaling pathway. In the presence of AKT inhibitor VIII, a pan-AKT inhibitor, ART reduced more cell proliferation, migration and invasion than in the absence of AKT inhibitor VIII, suggesting combination of ART and AKT inhibitor enhanced the anti-cancer effects of ART. Furthermore, the in vivo xenograft tumor model results suggested that ART decreased tumor size and weight, and suppressed AKT signaling. Taken together, our results indicated that ART inhibited ccRCC cell proliferation, colony formation, migration, invasion and tumorigenesis. Combination of ART and AKT inhibitor enhanced the anti-cancer cell proliferation, migration and invasion.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2019 Aug 30 [Epub]
Congcong Yu, Peiyu Sun, Yuehong Zhou, Bin Shen, Meihua Zhou, Lingzhi Wu, Min Kong
Department of Pharmacy, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing 314000, China., Department of Anesthesiology, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing 314000, China. Electronic address: .