Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway

白鲜碱通过阻断 PI3K/AKT 信号通路抑制胰腺癌细胞生长和上皮间质转化

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作者:Zhi-Qiang Zhang, Wen-Liang Xuan, Yang Huang, Shuo Ren, Tu-Ya Wulan, Ye Song, Dong-Bo Xue, Wei-Hui Zhang

Abstract

Many different treatments are available for pancreatic cancer (PC), including surgical resection, chemotherapy, radiotherapy, and immunotherapy, but these treatments are often ineffective at curing PC. Hence, identifying new and effective agents or strategies to improve therapeutic effects is critical. This study focused on the efficacy of dictamnine (DTM), a furan quinoline alkaloid extracted from Dictamnus dasycarpus Turcz., in treating PC. Our in vitro results showed that DTM can mitigate cell proliferation and induce cell cycle arrest and apoptosis in two different human PC cell lines. Moreover, epithelial-mesenchymal transition (EMT) was prevented during DTM treatment, reflected by reduced cell migration and invasion abilities. In vivo studies demonstrated that DTM treatment led to a remarkable inhibition of tumor growth in a xenograft nude mouse model. Mechanistic investigation showed that DTM might act by restraining constitutive and induced PI3K/AKT activity. In summary, our results demonstrated that DTM slows PC progression by inhibiting the activity of the PI3K/AKT signaling pathway and its downstream effectors and that DTM is effective as a pathway-specific cancer therapy. These findings could provide a greater understanding of the function of anticancer drugs and new options for PC treatment.

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