Identification of a novel inhibitor of liver cancer cell invasion and proliferation through regulation of Akt and Twist1

通过调节 Akt 和 Twist1 鉴定一种抑制肝癌细胞侵袭和增殖的新型抑制剂

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作者:Jain Ha #, Sewoong Lee #, Jiyoung Park, Jihye Seo, Eunjeong Kang, Haelim Yoon, Ba Reum Kim, Hyeon Kyu Lee, Seong Eon Ryu, Sayeon Cho

Abstract

When primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial-mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.

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