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

RPS inhibited the viability, migration, and invasion of esophageal cancer cells.A. RPS inhibited the viability of esophageal cancer cells. After overnight incubation, cells in 96-well plates were treated with RPS at 0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, or 60 μg/mL for 48 hours and then incubated with 20 μL of MTT (5mg/mL) for 4 hours. The absorbance at 550 nm was measured in a microplate reader. The percentage of viability relative to the controls without RPS was calculated. Each concentration was tested with 6 repeats in each experiment, n = 3. B. RPS reduced the invasion of esophageal cancer cells. Cells were cultured in the transwell chamber (5 x 104/chamber, 8 μm pore size and coated with 1mg/mL matrigel) containing serum-free media with RPS at 0, 5, 10, or 20 μg/mL in the upper chamber and RPMI-1640 medium + 10% FCS in the lower chambers for 48 h. The penetrated cells at the lower surface of the filter were fixed and counted under a microscope. A total of 5 fields of each chamber were randomly selected and the average cell number of the 5 fields was used, n = 3. * and # represents significant difference at 5, 10, and 20 μg/mL of RPS compared to 0 μg/mL of RPS in EC9706 cell and KYSE150 cells, respectively, P < 0.01. C. Images of wound healing of EC9706 cells, 20 x. D. Images of wound healing of KYSE150 cells, 20 x. E. RPS reduced the migration of EC9706 cells. F. RPS reduced the migration of KYSE150 cells. A total of 5 scratches were used for each concentration of RPS. Cells were cultured in serum-free media with RPS at 0, 3.25, 7.5, or 15 μg/mL for EC9706 cells, or at 0, 5, 10, or 20 μg/mL for KYSE150 for 24 h. Wounds were photographed under a phase-contrast inverted microscope, and the percentage gap closure was calculated as (width at 0h –width at 24 n)/width at 0h * 100%, n = 3. * represents significant difference between RPS at specified concentration vs 0 μg/mL, P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131560.g003: RPS inhibited the viability, migration, and invasion of esophageal cancer cells.A. RPS inhibited the viability of esophageal cancer cells. After overnight incubation, cells in 96-well plates were treated with RPS at 0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, or 60 μg/mL for 48 hours and then incubated with 20 μL of MTT (5mg/mL) for 4 hours. The absorbance at 550 nm was measured in a microplate reader. The percentage of viability relative to the controls without RPS was calculated. Each concentration was tested with 6 repeats in each experiment, n = 3. B. RPS reduced the invasion of esophageal cancer cells. Cells were cultured in the transwell chamber (5 x 104/chamber, 8 μm pore size and coated with 1mg/mL matrigel) containing serum-free media with RPS at 0, 5, 10, or 20 μg/mL in the upper chamber and RPMI-1640 medium + 10% FCS in the lower chambers for 48 h. The penetrated cells at the lower surface of the filter were fixed and counted under a microscope. A total of 5 fields of each chamber were randomly selected and the average cell number of the 5 fields was used, n = 3. * and # represents significant difference at 5, 10, and 20 μg/mL of RPS compared to 0 μg/mL of RPS in EC9706 cell and KYSE150 cells, respectively, P < 0.01. C. Images of wound healing of EC9706 cells, 20 x. D. Images of wound healing of KYSE150 cells, 20 x. E. RPS reduced the migration of EC9706 cells. F. RPS reduced the migration of KYSE150 cells. A total of 5 scratches were used for each concentration of RPS. Cells were cultured in serum-free media with RPS at 0, 3.25, 7.5, or 15 μg/mL for EC9706 cells, or at 0, 5, 10, or 20 μg/mL for KYSE150 for 24 h. Wounds were photographed under a phase-contrast inverted microscope, and the percentage gap closure was calculated as (width at 0h –width at 24 n)/width at 0h * 100%, n = 3. * represents significant difference between RPS at specified concentration vs 0 μg/mL, P < 0.01.

Mentions: To investigate the molecular mechanism underlying RPS-mediated inhibition of esophageal cancer development, we first examined the effects of RPS on the behavior of esophageal cancer cells. Our results show that RPS treatment significantly inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose-dependent manner (Fig 3, P < 0.01).


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 inhibited the viability, migration, and invasion of esophageal cancer cells.A. RPS inhibited the viability of esophageal cancer cells. After overnight incubation, cells in 96-well plates were treated with RPS at 0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, or 60 μg/mL for 48 hours and then incubated with 20 μL of MTT (5mg/mL) for 4 hours. The absorbance at 550 nm was measured in a microplate reader. The percentage of viability relative to the controls without RPS was calculated. Each concentration was tested with 6 repeats in each experiment, n = 3. B. RPS reduced the invasion of esophageal cancer cells. Cells were cultured in the transwell chamber (5 x 104/chamber, 8 μm pore size and coated with 1mg/mL matrigel) containing serum-free media with RPS at 0, 5, 10, or 20 μg/mL in the upper chamber and RPMI-1640 medium + 10% FCS in the lower chambers for 48 h. The penetrated cells at the lower surface of the filter were fixed and counted under a microscope. A total of 5 fields of each chamber were randomly selected and the average cell number of the 5 fields was used, n = 3. * and # represents significant difference at 5, 10, and 20 μg/mL of RPS compared to 0 μg/mL of RPS in EC9706 cell and KYSE150 cells, respectively, P < 0.01. C. Images of wound healing of EC9706 cells, 20 x. D. Images of wound healing of KYSE150 cells, 20 x. E. RPS reduced the migration of EC9706 cells. F. RPS reduced the migration of KYSE150 cells. A total of 5 scratches were used for each concentration of RPS. Cells were cultured in serum-free media with RPS at 0, 3.25, 7.5, or 15 μg/mL for EC9706 cells, or at 0, 5, 10, or 20 μg/mL for KYSE150 for 24 h. Wounds were photographed under a phase-contrast inverted microscope, and the percentage gap closure was calculated as (width at 0h –width at 24 n)/width at 0h * 100%, n = 3. * represents significant difference between RPS at specified concentration vs 0 μg/mL, P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131560.g003: RPS inhibited the viability, migration, and invasion of esophageal cancer cells.A. RPS inhibited the viability of esophageal cancer cells. After overnight incubation, cells in 96-well plates were treated with RPS at 0, 2.5, 5, 7.5, 10, 15, 20, 30, 40, or 60 μg/mL for 48 hours and then incubated with 20 μL of MTT (5mg/mL) for 4 hours. The absorbance at 550 nm was measured in a microplate reader. The percentage of viability relative to the controls without RPS was calculated. Each concentration was tested with 6 repeats in each experiment, n = 3. B. RPS reduced the invasion of esophageal cancer cells. Cells were cultured in the transwell chamber (5 x 104/chamber, 8 μm pore size and coated with 1mg/mL matrigel) containing serum-free media with RPS at 0, 5, 10, or 20 μg/mL in the upper chamber and RPMI-1640 medium + 10% FCS in the lower chambers for 48 h. The penetrated cells at the lower surface of the filter were fixed and counted under a microscope. A total of 5 fields of each chamber were randomly selected and the average cell number of the 5 fields was used, n = 3. * and # represents significant difference at 5, 10, and 20 μg/mL of RPS compared to 0 μg/mL of RPS in EC9706 cell and KYSE150 cells, respectively, P < 0.01. C. Images of wound healing of EC9706 cells, 20 x. D. Images of wound healing of KYSE150 cells, 20 x. E. RPS reduced the migration of EC9706 cells. F. RPS reduced the migration of KYSE150 cells. A total of 5 scratches were used for each concentration of RPS. Cells were cultured in serum-free media with RPS at 0, 3.25, 7.5, or 15 μg/mL for EC9706 cells, or at 0, 5, 10, or 20 μg/mL for KYSE150 for 24 h. Wounds were photographed under a phase-contrast inverted microscope, and the percentage gap closure was calculated as (width at 0h –width at 24 n)/width at 0h * 100%, n = 3. * represents significant difference between RPS at specified concentration vs 0 μg/mL, P < 0.01.
Mentions: To investigate the molecular mechanism underlying RPS-mediated inhibition of esophageal cancer development, we first examined the effects of RPS on the behavior of esophageal cancer cells. Our results show that RPS treatment significantly inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose-dependent manner (Fig 3, P < 0.01).

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