Chemosensitizing Effect of Astragalus Polysaccharides on Nasopharyngeal Carcinoma Cells by Inducing Apoptosis and Modulating Expression of Bax/Bcl-2 Ratio and Caspases

Abstract

BACKGROUND Platinum-based chemotherapy is the most effective regimen for nasopharyngeal carcinoma, which presents highly invasive and metastatic activity. However, the dose-related toxicity of chemotherapy agents limits the dose administration. Astragalus polysaccharide (APS) is the major active ingredient extracted from Chinese herb Radix Astragali and is proven to be active against carcinomas. We aimed to assess the chemosensitizing effects of Astragalus polysaccharides on nasopharyngeal carcinoma in vitro and in vivo and to explore the underlying mechanism. MATERIAL AND METHODS We used BALB/c nu/nu mice and human nasopharyngeal carcinoma cell lines CNE-1, CNE-2, and SUNE-1. MTT, Annexin V/PI, Western blot analysis, and TUNEL assay were carried out. RESULTS APS significantly promoted anti-proliferative and apoptotic effects of cisplatin on nasopharyngeal carcinoma cells. APS also enhanced the anti-tumor effects and cisplatin-induced apoptosis in the xenograft model. The level of Bcl-2 decreased, while the levels of Bax, caspase-3, and caspase-9 increased in cisplatin combined with APS treatment compared to cisplatin only treatment. The ratio of Bax to Bcl-2 was significantly enhanced by the APS to cisplatin. CONCLUSIONS APS enhanced the anti-proliferative and apoptotic effect of cisplatin by modulating expression of Bax/Bcl-2 ratio and caspases on nasopharyngeal carcinoma cells and in the xenograft model.

Figure 1

Anti-proliferative activity of APS on NPC cell lines CNE-1, CNE-2 and SUNE-1.

Figure 2

APS enhanced cisplatin sensitivity on NPC cell lines CNE-1, CNE-2, and SUNE-1 with increasing doses. * Statistically significant difference (P<0.01) between the Cisplatin+APS groups and the cisplatin treatment group.

Figure 3

APS enhanced cisplatin-induced apoptosis on NPC cell lines CNE-1, CNE-2 and SUNE-1. * Statistically significant difference (P<0.01) between the Cisplatin+APS group and the cisplatin treatment group.

Figure 4

APS increased cisplatin-induced protein expressions of Bcl-2, Bax, caspase-3, and caspase-9 on NPC cell lines CNE-1, CNE-2, and SUNE-1. (A) Cisplatin combined with APS decreased the expressions of Bcl-2 and increased the expression of Bax, caspase-3, and caspase-9 compared to cisplatin only treatment and control, as determined by Western blot analysis. (B) The ratio of Bax/Bcl-2 of each group. * Statistically significant difference (P<0.01) between the Cisplatin+APS group and the cisplatin treatment group.

Figure 5

APS enhanced cisplatin sensitivity on tumor volumes and weight of CNE-2 xenograft. * Statistically significant difference (P<0.01) between the Cisplatin+APS group and the cisplatin treatment group.

Figure 6

APS enhanced cisplatin-induced apoptosis of CNE-2 xenograft. * Statistically significant difference (P<0.01) between the Cisplatin+APS group and the cisplatin treatment group.

Figure 7

The effects of cisplatin combined with APS on the levels of Bcl-2, Bax, caspase-3, and caspase-9 expressions and the ratio of Bax/Bcl-2 in tumor tissues. * Statistically significant difference (P<0.01) between the Cisplatin+APS group and the cisplatin treatment group.