Limits...
Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway.

Yan S, Tian S, Kang Q, Xia Y, Li C, Chen Q, Zhang S, Li Z - PLoS ONE (2015)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.

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.

No MeSH data available.


Related in: MedlinePlus

The schematic diagram of the experimental design for NMBA injection and RPS administration.A. A schematic representation of experimental protocol. The empty arrows indicate subcutaneous injection of saline. The solid arrows indicate subcutaneous injection of NMBA. The shaded area represents oral RPS administration. B. The chemical formula of RPS. The letter “R” indicates that different functional groups can be at that position, resulting in different types of RPS with various molecular structures.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493120&req=5

pone.0131560.g001: The schematic diagram of the experimental design for NMBA injection and RPS administration.A. A schematic representation of experimental protocol. The empty arrows indicate subcutaneous injection of saline. The solid arrows indicate subcutaneous injection of NMBA. The shaded area represents oral RPS administration. B. The chemical formula of RPS. The letter “R” indicates that different functional groups can be at that position, resulting in different types of RPS with various molecular structures.

Mentions: Male F344 rats were randomly divided into the following 3 groups (n = 10 per group): healthy control group in which rats were subcutaneously injected with saline containing the same amount of DMSO as that used for rats exposed to NMBA; NMBA group in which rats were subcutaneously injected with NMBA at 1 mg/kg; NMBA + RPS group in which rats were subcutaneously injected with NMBA at 1 mg/kg and orally administered with RPS. The experimental design for the establishment of the rat model and RPS administration are illustrated in Fig 1. Briefly, rats in NMBA and NMBA + RPS groups were subcutaneously injected with 1 mg/kg NMBA 5 times per week for 5 weeks and then with a reduced frequency at 1 mg/kg NMBA once per week for another 5 weeks. Rat body weight was recorded twice per week for 14 weeks. Two rats in NMBA + RPS group died at week-10 and week-15, respectively, due to wrongly administer RPS into the airway. All other animals survived and were sacrificed at the end of 24 weeks via administration of chloral hydrate (3 mL/kg). Esophagus was excised and examined under a light microscope. Tumors larger than 1mm in diameter were counted. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52. Part of esophageal tissues were fixed in 10% formalin solution and embedded in paraffin for H&E staining, the rest of the tissues were frozen in liquid nitrogen for other experiment, such as western blot. RPS at 350 mg/kg or 100 mg/kg was administered by orally gavage once daily for 24 weeks starting at the first injection of NMBA.


Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway.

Yan S, Tian S, Kang Q, Xia Y, Li C, Chen Q, Zhang S, Li Z - PLoS ONE (2015)

The schematic diagram of the experimental design for NMBA injection and RPS administration.A. A schematic representation of experimental protocol. The empty arrows indicate subcutaneous injection of saline. The solid arrows indicate subcutaneous injection of NMBA. The shaded area represents oral RPS administration. B. The chemical formula of RPS. The letter “R” indicates that different functional groups can be at that position, resulting in different types of RPS with various molecular structures.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493120&req=5

pone.0131560.g001: The schematic diagram of the experimental design for NMBA injection and RPS administration.A. A schematic representation of experimental protocol. The empty arrows indicate subcutaneous injection of saline. The solid arrows indicate subcutaneous injection of NMBA. The shaded area represents oral RPS administration. B. The chemical formula of RPS. The letter “R” indicates that different functional groups can be at that position, resulting in different types of RPS with various molecular structures.
Mentions: Male F344 rats were randomly divided into the following 3 groups (n = 10 per group): healthy control group in which rats were subcutaneously injected with saline containing the same amount of DMSO as that used for rats exposed to NMBA; NMBA group in which rats were subcutaneously injected with NMBA at 1 mg/kg; NMBA + RPS group in which rats were subcutaneously injected with NMBA at 1 mg/kg and orally administered with RPS. The experimental design for the establishment of the rat model and RPS administration are illustrated in Fig 1. Briefly, rats in NMBA and NMBA + RPS groups were subcutaneously injected with 1 mg/kg NMBA 5 times per week for 5 weeks and then with a reduced frequency at 1 mg/kg NMBA once per week for another 5 weeks. Rat body weight was recorded twice per week for 14 weeks. Two rats in NMBA + RPS group died at week-10 and week-15, respectively, due to wrongly administer RPS into the airway. All other animals survived and were sacrificed at the end of 24 weeks via administration of chloral hydrate (3 mL/kg). Esophagus was excised and examined under a light microscope. Tumors larger than 1mm in diameter were counted. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52. Part of esophageal tissues were fixed in 10% formalin solution and embedded in paraffin for H&E staining, the rest of the tissues were frozen in liquid nitrogen for other experiment, such as western blot. RPS at 350 mg/kg or 100 mg/kg was administered by orally gavage once daily for 24 weeks starting at the first injection of NMBA.

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Departments of Pharmacology, Nankai Hospital, Tianjin, P. R. China.

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.

No MeSH data available.


Related in: MedlinePlus