title: Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway.
abstract: Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1 mg/kg) for 10 weeks. RPS (350 mg/kg or 100 mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.
authors.affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yan
authors.affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Tian
authors.affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Institute of Integrative Medicine Therapy for Acute Abdominal Diseases of Tianjin, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Taizhou Hospital, Taizhou City, Zhejiang Province, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Integrative Medicine Therapy for Acute Abdominal Diseases of Tianjin, Nankai Hospital, Tianjin, P. R. China.
authors.forename: Shukun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Nankai Hospital, Nankai District, Tianjin, P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000009:adverse effects / Q000031:analogs & derivatives*; D015232:Dinoprostone / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D027343:Rhizome / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D012503:Saponins; D019938:Cyclin D1; C014707:nitrosobenzylmethylamine; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D004128:Dimethylnitrosamine