Physalin B inhibits cell proliferation and induces apoptosis in undifferentiated human gastric cancer HGC-27 cells

Physalin B inhibits cell proliferation and induces apoptosis in undifferentiated human gastric cancer HGC-27 cells
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Physalin B 抑制未分化人胃癌 HGC-27 细胞增殖并诱导细胞凋亡

DOI:
10.1111/ajco.13593
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发表时间:
2021-06-23
影响因子:
1.9
通讯作者:
Zeng, Chengwu
Zeng, Chengwu
中科院分区:
医学4区
文献类型:
--
作者:
Fang, Chunsheng;Chen, Cunte;Zeng, Chengwu

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酸浆中酸浆素B(PB)的研究背景(茄科)是一种天然存在的开环甾类化合物,具有多种生物活性,包括抗炎和抗癌活性。然而,PB在人胃癌(GC)细胞中的作用和机制尚未得到很好的表征。方法用PB处理未分化胃癌细胞株HGC-27和半分化胃癌细胞株SGC-7901。进行细胞计数试剂盒-8(CCK-8)和集落形成试验以评价细胞活力。Annexin V/PI和PI/RNase DNA染色法分别检测细胞凋亡和细胞周期,Western blotting法检测蛋白表达。结果PB对HGC-27细胞的增殖有明显的抑制作用,且呈剂量和时间依赖性。PB可诱导HGC-27细胞G 0/G1期阻滞和caspase依赖性凋亡。PB可诱导HGC-27细胞中切割型半胱天冬酶8、3和7、聚腺苷二磷酸核糖聚合酶(PARP)和细胞周期蛋白依赖性激酶(CDK)抑制剂p-Chk 2的表达,而细胞周期相关蛋白cyclin D1、cyclin D3、CDK 4、CDK 6、cyclin E和磷酸化视网膜母细胞瘤肿瘤抑制蛋白(p-Rb)的表达呈剂量依赖性下调。结论PB可通过cyclin-dependent kinase抑制HGC-27细胞增殖,并诱导caspase-dependent凋亡,提示PB可能是治疗未分化胃癌的一种有效药物。
Background Physalin B (PB) from Physalis angulata L. (Solanaceae) is a naturally occurring secosteroid with multiple biological activities, including anti-inflammatory and anticancer activity. However, PB's effects and mechanisms in human gastric cancer (GC) cells are not well characterized. Methods The undifferentiated GC cell line HGC-27 and semi-differentiated GC cell line SGC-7901 were treated with PB. Cell counting kit-8 (CCK-8) and colony formation assays were performed to evaluate cell viability. Apoptosis and the cell cycle were assessed by Annexin V/PI and PI/RNase DNA staining assays, respectively, and Western blotting was used to evaluate the expression of a protein. Results PB significantly inhibited the proliferation of HGC-27 cells in a dose- and time-dependent manner. Moreover, PB induced G0/G1 cycle arrest and caspase-dependent apoptosis of HGC-27 cells. Cleaved caspases 8, 3, and 7, poly(ADP)-ribose polymerase (PARP), and the cyclin-dependent kinase (CDK) inhibitor p-Chk2 was induced by PB in HGC-27 cells, while the cell cycle-related proteins cyclin D1, cyclin D3, CDK4, CDK6, cyclin E, and phosphorylated retinoblastoma tumor suppressor protein (p-Rb) were downregulated in a dose-dependent manner. Conclusions PB inhibits proliferation via cyclin-dependent kinase and induces caspase-dependent apoptosis in HGC-27 cells, suggesting that PB might be a novel and effective agent for undifferentiated GC therapy.