Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
Xiang‐Peng Tan,
Yan He,
Yun‐Na Huang,
Can‐Can Zheng,
Jun‐Qi Li,
Qin‐Wen Liu,
Ming‐Liang He,
Bin Li,
Wen‐Wen Xu
Affiliations
Xiang‐Peng Tan
MOE Key Laboratory of Tumor Molecular Biology National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology and The First Affiliated Hospital of Jinan University Jinan University Guangzhou China
Yan He
MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology Jinan University Guangzhou China
Yun‐Na Huang
MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology Jinan University Guangzhou China
Can‐Can Zheng
MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes Institute of Life and Health Engineering College of Life Science and Technology Jinan University Guangzhou China
Jun‐Qi Li
MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology Jinan University Guangzhou China
Qin‐Wen Liu
MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology Jinan University Guangzhou China
Ming‐Liang He
Department of Biomedical Sciences City University of Hong Kong Hong Kong China
Bin Li
MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes Institute of Life and Health Engineering College of Life Science and Technology Jinan University Guangzhou China
Wen‐Wen Xu
MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic Medicine Institute of Biomedicine College of Life Science and Technology Jinan University Guangzhou China
Abstract Colorectal cancer (CRC) is one of the most common malignancies currently. Despite advances in drug development, the survival and response rates in CRC patients are still poor. In our previous study, a library comprised of 1056 bioactive compounds was used for screening of drugs that could suppress CRC. Lomerizine 2HCl, which is an approved prophylactic drug for migraines, was selected for our studies. The results of in vitro and in vivo assays suggested that lomerizine 2HCl suppresses cell growth and promotes apoptosis in CRC cells. Moreover, lomerizine 2HCl inhibits cell migration and invasion of CRC. RNA sequencing analysis and Western blotting confirmed that lomerizine 2HCl can inhibit cell growth, migration, and invasion through PI3K/AKT/mTOR signaling pathway and induces protective autophagy in CRC. Meanwhile, autophagy inhibition by 3‐methyladenine (3‐MA) increases lomerizine 2HCl‐induced cell apoptosis. Taken together, these results imply that lomerizine 2HCl is a potential anticancer agent, and the combination of lomerizine 2HCl and autophagy inhibitors may serve as a novel strategy to increase the antitumor efficacy of agents in the treatment of CRC.
