Hui-Ning Fan1, Mei-Ying Zhu1, Shi-Qiao Peng1, Jin-Shui Zhu2, Jing Zhang3, Guo-Qiang Qu4. 1. Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 2. Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zhujs1803@163.com. 3. Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: jing5522724@163.com. 4. Department of Gastroenterology, Shanghai University of Medicine and Health Sciences Affiliated Sixth People's Hospital East Campus, Shanghai 201603, China. Electronic address: qgqahtl@163.com.
Abstract
BACKGROUND: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. MATERIAL AND METHODS: The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. RESULTS: We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. CONCLUSIONS: DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.
BACKGROUND:Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. MATERIAL AND METHODS: The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. RESULTS: We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. CONCLUSIONS:DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.