7 8 7 4 4

论文已发表


注册即可获取德孚的最新动态



IF 收录期刊





更多详情 >>



作者优惠计划

Favored Author Program


很高兴为我们的作者提供一种切实的方法以支持开放获取,并鼓励教师和研究人员通过开放获取模式,尽可能广泛地推广他们的作品。


作者优惠计划的成员将获得:


文章发表费(APC) 10% 的折扣


这 10% 的折扣从您加入 “作者优惠计划” 之时开始,并将适用于之后提交的所有论文



*若要加入“作者优惠计划”,您需要已经在德孚医药出版社发表过论文,或为我们进行过同行评审。作者必须在提交论文之前注册该优惠计划,折扣不能追溯应用于已提交的论文




更多详情 >>



已发表论文

由于自噬能力的增加,厄洛替尼 (Erlotinib) 和 PARP 抑制剂的组合可以抑制 A2780 肿瘤异种移植物的生长

 

Authors Sui H, Shi C, Yan Z, Li H

Published Date June 2015 Volume 2015:9 Pages 3183—3190

DOI http://dx.doi.org/10.2147/DDDT.S82035

Received 2 February 2015, Accepted 9 March 2015, Published 22 June 2015

Approved for publication by Dr Wei Duan

Background: Ovarian cancer is the leading cause of death in women with gynecological malignancy worldwide. Despite multiple new approaches to treatment, relapse remains almost inevitable in patients with advanced disease. The poor outcome of advanced ovarian cancer treated with conventional therapy stimulated the search for new strategies to improve therapeutic efficacy. Although epidermal growth factor receptor (EGFR) and poly(ADP-ribose) polymerase (PARP) inhibitors have known activity in advanced ovarian cancer, the effect of combined therapy against EGFR and PARP in this population has not been reported. In the current study, we investigated the mechanisms of erlotinib used alone or in combination with olaparib (AZD2281), a potent inhibitor of PARP, in an EGFR-overexpressing ovarian tumor xenograft model.
Methods: A2780 (EGFR-overexpressing, BRCA1/2  wild-type) cells were subcutaneously injected into nude mice, which were then randomly assigned to treatment with vehicle, erlotinib, AZD2281, or erlotinib + AZD2281, for up to 3 weeks. All mice were then sacrificed and tumor tissues were subjected to Western blot analysis and monodansylcadervarine staining (for analysis of autophagy).
Results: Erlotinib could slightly inhibit growth of A2780 tumor xenografts, and AZD2281 alone had similar effects on tumor growth. However, the combination treatment had a markedly enhanced antitumor effect. Western blot analysis revealed that treatment with erlotinib could significantly reduce the phosphorylation level of ERK1/2 and AKT in A2780 tumor tissue. Of interest, monodansylcadervarine staining showed that the autophagic effects were substantially enhanced when the agents were combined, which may be due to downregulation of apoptosis.
Conclusion: These results suggest that combination of a selective EGFR inhibitor and a PARP inhibitor is effective in ovarian cancer A2780 xenografts, and depends on enhanced autophagy.
Keywords: erlotinib, poly(ADP-ribose) polymerase, PARP, olaparib, tyrosine kinase inhibitor, ovarian cancer, autophagy, apoptosis