Cancer Management and Research (Apr 2020)
Astragalus Polysaccharide Promotes Adriamycin-Induced Apoptosis in Gastric Cancer Cells
Abstract
Jie Song,1,* Youming Chen,2,* Donghong He,1,* Wenhui Tan,1 Fang Lv,1 Biao Liang,1 Tingting Xia,3 Jing Li1,4 1Center of Digestive Endoscopy, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Li; Tingting Xia Email [email protected]; [email protected]: Astragalus polysaccharide (APS), a common Chinese herbal compound extracted from Astragalus membranaceus, has been proposed to increase the tumour response of and stabilize chemotherapy drugs while reducing their toxicity. Here, we examined the effects of APS on apoptosis in gastric cancer (GC) cells in the presence or absence of adriamycin (0.1 μg/mL).Methods: GC cells cultured in the presence or absence of adriamycin (0.1 μg/mL) were administered APS (50– 200 μg/mL) for 24– 72 h and subjected to an MTT assay to examine cell viability. Active caspase-3 expression and DNA fragmentation were assessed to evaluate apoptosis, and real-time PCR was used to analyse the expression levels of multidrug resistance (MDR1) genes and tumour suppressor genes. Western blot analysis was applied to detect cleaved caspase-3 and phosphorylated AMPK (p-AMPK).Results: Cellular viability was profoundly reduced by APS, and GC cell apoptosis was strongly increased by APS in a time- and dose-dependent manner; these changes may be linked to an increase in p-AMPK levels because the AMPK inhibitor compound C blocked the effects of APS. Similarly, adriamycin-induced decreases in cellular viability and apoptosis of GC cells were enhanced by APS administration. The expression of tumour suppressor genes (SEMA3F, P21WAF1/CIP1, FBXW7), but not of MDR1, was increased by APS compared to the control, and p-AMPK levels were lower in adriamycin-resistant GC cells than in either adriamycin-sensitive GC cells or an immortalized human gastric epithelial cell line.Conclusion: APS induces apoptosis independently and strengthens the proapoptotic effect of adriamycin on GC cells, suggesting that APS may act as a chemotherapeutic sensitizer.Keywords: Astragalus polysaccharide, gastric cancer, apoptosis, chemotherapy
