Guirong Zheng1, Zhichun Shen1, Hongning Chen1, Jian Liu1, Kai Jiang1, Lulu Fan1, Lee Jia1, Jingwei Shao2. 1. Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350116, China. 2. Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350116, China. Electronic address: shaojingwei@fzu.edu.cn.
Abstract
BACKGROUND: Metastasis is the key phase of cancer progression that characterizes a more advanced stage and a poorer prognosis. The majority of cancer fatalities occur as a consequence of metastasis. OBJECTIVE: Mifepristone (RU486), a chemical abortifacient, has recently been used in clinical trials for psychotic depression and cancer chemotherapy. As the most predominant biological active metabolite of mifepristone, metapristone is being developed as a novel cancer metastasis chemopreventive agent by us. However, there is no information available to address the effects of metapristone on non-small cell lung cancer (NSCLC). The aim of our study was to investigate the inhibitory effect of metapristone on the proliferation and metastasis of NSCLC cells. METHOD: In the present study, we evaluated the efficacy of metapristone on the growth, migration and invasion in different kinds of NSCLC cells (A549, H1975 and H1299), and further investigated the underlying mechanism of metapristone by real time PCR and western blot assay. RESULTS: Metapristone could significantly inhibit the proliferation, migration and invasion of NSCLC cells through suppressing RAS/RAF/MEK/MAPK and PI3K/AKT signaling pathways. Moreover, metapristone could effectively inhibit the formation of NSCLC cells' cytoskeleton in a concentration-dependent manner, which possibly led to the inhibition of NSCLC cells' migration. CONCLUSION: Overall, it was preliminarily demonstrated that metapristone could be developed as a useful agent to show anti-metastasis activity for NSCLC.
BACKGROUND: Metastasis is the key phase of cancer progression that characterizes a more advanced stage and a poorer prognosis. The majority of cancer fatalities occur as a consequence of metastasis. OBJECTIVE:Mifepristone (RU486), a chemical abortifacient, has recently been used in clinical trials for psychotic depression and cancer chemotherapy. As the most predominant biological active metabolite of mifepristone, metapristone is being developed as a novel cancer metastasis chemopreventive agent by us. However, there is no information available to address the effects of metapristone on non-small cell lung cancer (NSCLC). The aim of our study was to investigate the inhibitory effect of metapristone on the proliferation and metastasis of NSCLC cells. METHOD: In the present study, we evaluated the efficacy of metapristone on the growth, migration and invasion in different kinds of NSCLC cells (A549, H1975 and H1299), and further investigated the underlying mechanism of metapristone by real time PCR and western blot assay. RESULTS:Metapristone could significantly inhibit the proliferation, migration and invasion of NSCLC cells through suppressing RAS/RAF/MEK/MAPK and PI3K/AKT signaling pathways. Moreover, metapristone could effectively inhibit the formation of NSCLC cells' cytoskeleton in a concentration-dependent manner, which possibly led to the inhibition of NSCLC cells' migration. CONCLUSION: Overall, it was preliminarily demonstrated that metapristone could be developed as a useful agent to show anti-metastasis activity for NSCLC.