Ginsenoside Rg3 enhances the anti- proliferative activity of erlotinib in pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling pathway
Ginsenoside Rg3 enhances the anti- proliferative activity of erlotinib in pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling pathway
复制标题
人参皂苷Rg3通过下调EGFR/PI3K/Akt信号通路增强厄洛替尼对胰腺癌细胞的抗增殖活性
DOI：
10.1016/j.biopha.2017.10.043
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发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Fei, Zhenghua
中科院分区：
文献类型：
--
作者：
Jiang, Jin;Yuan, Zuguo;Fei, Zhenghua
厄洛替尼在胰腺癌的治疗中显示出活性。然而，由于EGFR非依赖性PI 3 K/Akt信号通路，EGFR阻断的益处有限。研究表明人参皂苷Rg 3对多种肿瘤的PI 3 K-Akt信号通路有较强的抑制作用。我们的目的是研究人参皂苷Rg 3的活性，增敏厄洛替尼在体外和体内治疗胰腺癌。使用人胰腺癌细胞系BxPC-3和AsPC-1。通过细胞增殖和集落形成实验、Annexin V/PI凋亡分析、Western blot分析、免疫组化和体内实验研究。人参皂苷Rg 3可增强厄洛替尼对胰腺癌BxPC-3和AsPC-1细胞及移植瘤的抗增殖作用。人参皂苷Rg 3增强厄洛替尼诱导的细胞凋亡，并增加caspase-3，9和PARP裂解的表达水平。厄洛替尼/人参皂苷Rg 3治疗显著降低了p-EGFR、p-PI 3 K和p-Akt表达水平。人参皂苷Rg 3可通过诱导胰腺癌细胞凋亡和下调EGFR/PI 3 K/AKT通路增强厄洛替尼抑制胰腺癌细胞增殖的作用。
Erlotinib has shown activity in the management of pancreatic cancer. However, the benefit of EGFR blockade is limited due to EGFR independent PI3K/Akt signaling pathway. Studies have reported that Ginsenoside Rg3 strongly inhibited PI3K-Akt signaling pathway of many carcinomas. We aimed to investigate the activity of Ginsenoside Rg3 to sensitize erlotinib in treating pancreatic cancer in vitro and in vivo. Human pancreatic cancer cell lines BxPC-3 and AsPC-1 were used. Cell proliferation and colony formation assay, Annexin V/PI apoptosis analysis, Western blot analysis, immunohistochemistry and in vivo study were carried out. Ginsenoside Rg3 enhanced the anti-proliferative effects of erlotinib in BxPC-3 and AsPC-1 pancreatic cancer cells and xenograft. Ginsenoside Rg3 enhanced erlotinib-induced apoptosis and increased caspase-3,9 and PARP cleavage expression levels. Erlotinib/Ginsenoside Rg3 treatment decreased the levels of p-EGFR, p-PI3K, and p-Akt expression significantly. Ginsenoside Rg3 could enhance the efficacy of erlotinib to inhibit the proliferation of pancreatic cancer cells via induction of apoptosis and downregulation of the EGFR/PI3K/AKT pathway.