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黄芪多糖促进阿霉素诱导的胃癌细胞凋亡。

Astragalus Polysaccharide Promotes Adriamycin-Induced Apoptosis in Gastric Cancer Cells.

作者信息

Song Jie, Chen Youming, He Donghong, Tan Wenhui, Lv Fang, Liang Biao, Xia Tingting, Li Jing

机构信息

Center of Digestive Endoscopy, Guangdong Second Provincial General Hospital, Guangzhou, People's Republic of China.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Apr 1;12:2405-2414. doi: 10.2147/CMAR.S237146. eCollection 2020.

Abstract

PURPOSE

polysaccharide (APS), a common Chinese herbal compound extracted from , 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, P21, 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.

摘要

目的

黄芪多糖(APS)是从黄芪中提取的一种常见的中药成分,有人提出它可以增强肿瘤对化疗药物的反应,稳定化疗药物,同时降低其毒性。在此,我们研究了在有或没有阿霉素(0.1μg/mL)存在的情况下,APS对胃癌(GC)细胞凋亡的影响。

方法

在有或没有阿霉素(0.1μg/mL)存在的情况下培养的GC细胞,给予APS(50-200μg/mL)处理24-72小时,并进行MTT试验以检测细胞活力。评估活性半胱天冬酶-3的表达和DNA片段化以评估细胞凋亡,并使用实时PCR分析多药耐药(MDR1)基因和肿瘤抑制基因的表达水平。应用蛋白质免疫印迹分析来检测裂解的半胱天冬酶-3和磷酸化的AMPK(p-AMPK)。

结果

APS显著降低细胞活力,并且以时间和剂量依赖性方式强烈增加GC细胞凋亡;这些变化可能与p-AMPK水平的增加有关,因为AMPK抑制剂化合物C阻断了APS的作用。同样,阿霉素诱导的GC细胞活力降低和凋亡通过给予APS而增强。与对照组相比,APS增加了肿瘤抑制基因(SEMA3F,P21,FBXW7)的表达,但没有增加MDR1的表达,并且阿霉素耐药的GC细胞中的p-AMPK水平低于阿霉素敏感的GC细胞或永生化人胃上皮细胞系。

结论

APS独立诱导凋亡并增强阿霉素对GC细胞的促凋亡作用,表明APS可能作为化疗增敏剂。

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