Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China.
Clinical Research Department of Chinese and Western Medicine, Jiangsu Province Institute of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China.
BMC Complement Altern Med. 2019 Jun 26;19(1):151. doi: 10.1186/s12906-019-2569-6.
Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo.
The viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR.
Costunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor.
Collectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.
从木香中提取的倍半萜内酯 Costunolide 具有多种抗癌活性。然而，Costunolide 对胃癌 (GC) 的作用仍存在争议。在这项研究中，我们研究了 Costunolide 在体外和体内诱导人胃腺癌 BGC-823 细胞凋亡的潜在机制。
MTT 法检测 BGC-823 细胞活力。流式细胞术分析 Costunolide 诱导 BGC-823 细胞凋亡和线粒体膜电位 (ΔΨm) 的变化。裸鼠异种移植模型评估 Costunolide 对人胃腺癌的抑制作用。Western blot 和 Q-PCR 检测凋亡相关蛋白和基因的表达。
Costunolide 呈时间和浓度依赖性抑制 BGC-823 细胞活力。Costunolide 显著诱导 BGC-823 细胞凋亡并降低 ΔΨm。Costunolide 增加 Bax、cleaved caspase 9、cleaved caspase 7、cleaved caspase 3 和 cleaved poly ADP ribose polymerase (PARP) 蛋白的表达，降低 Bcl-2、pro-caspase 9、pro-caspase 7、pro-caspase 3 和 PARP 蛋白的表达。Costunolide 上调 puma、Bak1 和 Bax mRNA 的表达，下调 Bcl-2 mRNA 的表达。此外，我们证明 Costunolide 抑制 BGC-823 细胞裸鼠异种移植瘤的生长并诱导其凋亡。Costunolide 增加 cleaved caspase 9、cleaved caspase 3 和 Bax 蛋白的表达，降低异种移植瘤中 Bcl-2 蛋白的表达。Costunolide 上调 puma 和 Bax mRNA 的表达，降低异种移植瘤中 Bcl-2 mRNA 的表达。
综上所述，我们的研究结果表明，Costunolide 诱导人胃腺癌 BGC-823 细胞线粒体介导的凋亡，可能成为临床治疗 GC 的候选药物。
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