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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

RPS reduced the size and number of tumors on the esophagus of rats exposed to NMBA.A. Photographs and H&E staining of esophageal tissues of rats from healthy control, NMBA, or NMBA+RPS group. Male F344 rats (n = 10 per group) were subcutaneously injected with saline containing DMSO (Healthy control group), NMBA at 1mg/kg (NMBA group), or NMBA plus oral administration of RPS at 350 mg/kg (NMBA + RPS group). Esophagus was dissected, photographed, and examined under a light microscope. Part of esophageal tissues was fixed in 10% formalin solution and stained with H&E. B. RPS significantly reduced the number of tumors on esophagus. Tumors larger than 1mm in diameter were counted, n = 10. C. RPS significantly decreased tumor size. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52, n = 10. D. RPS reduced the number of papilloma and carcinoma. Two pathologists, who were blinded for the treatment allocation, examined the type and number of tumors. The average number of papilloma and carcinoma is presented, n = 10. * represents significant difference between NMBA group vs healthy control group, P < 0.01. # represents significant difference between NMBA +RPS group vs NMBA group, P < 0.01.
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pone.0131560.g002: RPS reduced the size and number of tumors on the esophagus of rats exposed to NMBA.A. Photographs and H&E staining of esophageal tissues of rats from healthy control, NMBA, or NMBA+RPS group. Male F344 rats (n = 10 per group) were subcutaneously injected with saline containing DMSO (Healthy control group), NMBA at 1mg/kg (NMBA group), or NMBA plus oral administration of RPS at 350 mg/kg (NMBA + RPS group). Esophagus was dissected, photographed, and examined under a light microscope. Part of esophageal tissues was fixed in 10% formalin solution and stained with H&E. B. RPS significantly reduced the number of tumors on esophagus. Tumors larger than 1mm in diameter were counted, n = 10. C. RPS significantly decreased tumor size. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52, n = 10. D. RPS reduced the number of papilloma and carcinoma. Two pathologists, who were blinded for the treatment allocation, examined the type and number of tumors. The average number of papilloma and carcinoma is presented, n = 10. * represents significant difference between NMBA group vs healthy control group, P < 0.01. # represents significant difference between NMBA +RPS group vs NMBA group, P < 0.01.

Mentions: All 10 rats survived 10-week NMBA exposure and NMBA injection dramatically induced tumor development in the esophagus of the rats. The surface of esophagus in the rats exposed to NMBA was covered with tumor lesions with various sizes (Fig 2A). RPS at 350mg/kg significantly reduced the number (3.5 ± 1.58 vs 1.4 ± 1.11, P < 0.01, Fig 2A and 2B) and average size of tumors (17.71 ± 9.16 mm3 vs 6.47 ± 5.86 mm3, P < 0.01, Fig 2A and 2C) on the esophagus. Histopathological examination of the esophageal tissues revealed that NMBA exposure led to squamous epithelial hyperplasia (Fig 2A) and the numbers of papillomas and carcinomas of NMBA group were considerably higher than those of NMBA + RPS group although the differences between the 2 groups were not statistically significant (Fig 2D). Low-dose RPS (100mg/kg) did not affect tumor size (NMBA exposure group: 15.0±11.9 mm3 vs. NMBA + RPS group: 17.6±9.9 mm3, P > 0.05) and the number of tumors (NMBA exposure group: 3.5±1.0 vs. NMBA + RPS group: 3.3±1.6, P > 0.05) in the rats exposed to 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)

RPS reduced the size and number of tumors on the esophagus of rats exposed to NMBA.A. Photographs and H&E staining of esophageal tissues of rats from healthy control, NMBA, or NMBA+RPS group. Male F344 rats (n = 10 per group) were subcutaneously injected with saline containing DMSO (Healthy control group), NMBA at 1mg/kg (NMBA group), or NMBA plus oral administration of RPS at 350 mg/kg (NMBA + RPS group). Esophagus was dissected, photographed, and examined under a light microscope. Part of esophageal tissues was fixed in 10% formalin solution and stained with H&E. B. RPS significantly reduced the number of tumors on esophagus. Tumors larger than 1mm in diameter were counted, n = 10. C. RPS significantly decreased tumor size. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52, n = 10. D. RPS reduced the number of papilloma and carcinoma. Two pathologists, who were blinded for the treatment allocation, examined the type and number of tumors. The average number of papilloma and carcinoma is presented, n = 10. * represents significant difference between NMBA group vs healthy control group, P < 0.01. # represents significant difference between NMBA +RPS group vs NMBA group, P < 0.01.
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Related In: Results  -  Collection

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pone.0131560.g002: RPS reduced the size and number of tumors on the esophagus of rats exposed to NMBA.A. Photographs and H&E staining of esophageal tissues of rats from healthy control, NMBA, or NMBA+RPS group. Male F344 rats (n = 10 per group) were subcutaneously injected with saline containing DMSO (Healthy control group), NMBA at 1mg/kg (NMBA group), or NMBA plus oral administration of RPS at 350 mg/kg (NMBA + RPS group). Esophagus was dissected, photographed, and examined under a light microscope. Part of esophageal tissues was fixed in 10% formalin solution and stained with H&E. B. RPS significantly reduced the number of tumors on esophagus. Tumors larger than 1mm in diameter were counted, n = 10. C. RPS significantly decreased tumor size. The volume of the lesions was calculated using the standard formula: volume = length × width × height × 0.52, n = 10. D. RPS reduced the number of papilloma and carcinoma. Two pathologists, who were blinded for the treatment allocation, examined the type and number of tumors. The average number of papilloma and carcinoma is presented, n = 10. * represents significant difference between NMBA group vs healthy control group, P < 0.01. # represents significant difference between NMBA +RPS group vs NMBA group, P < 0.01.
Mentions: All 10 rats survived 10-week NMBA exposure and NMBA injection dramatically induced tumor development in the esophagus of the rats. The surface of esophagus in the rats exposed to NMBA was covered with tumor lesions with various sizes (Fig 2A). RPS at 350mg/kg significantly reduced the number (3.5 ± 1.58 vs 1.4 ± 1.11, P < 0.01, Fig 2A and 2B) and average size of tumors (17.71 ± 9.16 mm3 vs 6.47 ± 5.86 mm3, P < 0.01, Fig 2A and 2C) on the esophagus. Histopathological examination of the esophageal tissues revealed that NMBA exposure led to squamous epithelial hyperplasia (Fig 2A) and the numbers of papillomas and carcinomas of NMBA group were considerably higher than those of NMBA + RPS group although the differences between the 2 groups were not statistically significant (Fig 2D). Low-dose RPS (100mg/kg) did not affect tumor size (NMBA exposure group: 15.0±11.9 mm3 vs. NMBA + RPS group: 17.6±9.9 mm3, P > 0.05) and the number of tumors (NMBA exposure group: 3.5±1.0 vs. NMBA + RPS group: 3.3±1.6, P > 0.05) in the rats exposed to 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