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, 1mg/kg) for 10 weeks. RPS (350 mg/kg or 100mg/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.
Highlights
Esophageal cancer is the sixth leading cause of cancer death worldwide and the fourth in China [1, 2]
We found Rhizoma Paridis Saponins (RPS) significantly suppressed tumor development in a rat model of NMBA-induced esophageal cancer and inhibited the viability, migration, and invasion of human esophageal cancer cells EC9706 and KYSE150
Our study showed that RPS induced apoptosis in the esophageal cancer cells
Summary
Esophageal cancer is the sixth leading cause of cancer death worldwide and the fourth in China [1, 2]. In 2009, the incidence rate of the disease in China was 22.14/100,000 and reached even higher than 100/100,000 in some areas, such as Cixian in province Hebei [2, 3]. The mortality rate of esophageal cancer has decreased over past 30 years owing to the improvement of economy and changes of life style, esophageal cancer remains prevalent in rural area of China and in Chinese men [2, 3]. Surgical intervention is the primary treatment for esophageal cancer. Multimodal treatment with neoadjuvant chemotherapy or combined chemoradiotherapy followed by surgery has been recommended for locally advanced esophageal cancer [4]. Effective therapies for esophageal cancer are in urgent need
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