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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 promoted cell cycle G2/M phase arrest.Cells used for analyzing apoptosis were also analyzed for cell cycle using FlowJo software, 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.
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pone.0131560.g005: RPS promoted cell cycle G2/M phase arrest.Cells used for analyzing apoptosis were also analyzed for cell cycle using FlowJo software, 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.

Mentions: RPS-mediated inhibition of viability, migration, and invasion suggested that RPS might interfere in apoptosis and cell cycle in the esophageal cancer cells. Indeed, our flow cytometry results demonstrated that RPS at the concentration of 10 μg/mL or higher significantly increased the proportion of apoptotic cells in both EC9706 and KYSE150 cells (Fig 4, P < 0.01). Consistently, RPS at the same concentration markedly increased the proportion of cells in G2 phase (Fig 5, P < 0.01), suggesting that RPS treatment induce G2/M cell cycle arrest in the esophageal cancer cells. The proportion of EC9706 cells in S phase was not substantially affected by RPS, whereas RPS reduced the percentage of KYSE150 cells in S phase in a dose-dependent manner, indicating that KYSE 150 cell growth was inhibited by RPS (Fig 5). In addition, the expression of Cyclin D1 in the esophageal cancer cells was markedly reduced by RPS treatment (Fig 6A). We also examined Cyclin D1 expression in the esophageal tissues of rats. Compared with healthy control, NMBA exposure dramatically induced Cyclin D1 expression in the esophageal tissue; whereas RPS administration significantly reduced the NMBA-induced over-expression of Cyclin D1 (Fig 6B and 6C, P < 0.01). These results further support that RPS interferes in cell cycle in the esophageal cancer cells.


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 promoted cell cycle G2/M phase arrest.Cells used for analyzing apoptosis were also analyzed for cell cycle using FlowJo software, 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.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131560.g005: RPS promoted cell cycle G2/M phase arrest.Cells used for analyzing apoptosis were also analyzed for cell cycle using FlowJo software, 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.
Mentions: RPS-mediated inhibition of viability, migration, and invasion suggested that RPS might interfere in apoptosis and cell cycle in the esophageal cancer cells. Indeed, our flow cytometry results demonstrated that RPS at the concentration of 10 μg/mL or higher significantly increased the proportion of apoptotic cells in both EC9706 and KYSE150 cells (Fig 4, P < 0.01). Consistently, RPS at the same concentration markedly increased the proportion of cells in G2 phase (Fig 5, P < 0.01), suggesting that RPS treatment induce G2/M cell cycle arrest in the esophageal cancer cells. The proportion of EC9706 cells in S phase was not substantially affected by RPS, whereas RPS reduced the percentage of KYSE150 cells in S phase in a dose-dependent manner, indicating that KYSE 150 cell growth was inhibited by RPS (Fig 5). In addition, the expression of Cyclin D1 in the esophageal cancer cells was markedly reduced by RPS treatment (Fig 6A). We also examined Cyclin D1 expression in the esophageal tissues of rats. Compared with healthy control, NMBA exposure dramatically induced Cyclin D1 expression in the esophageal tissue; whereas RPS administration significantly reduced the NMBA-induced over-expression of Cyclin D1 (Fig 6B and 6C, P < 0.01). These results further support that RPS interferes in cell cycle in the esophageal cancer cells.

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