Xiaochao Zhu, Yinggang Xu, Xiangxin Zheng, Ying Li
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引用次数: 0
Abstract
Objective: To investigate the underlying mechanism of pertuzumab combined with pyrrolitinib in the treatment of breast cancer.
Methods: Real-time PCR and Western blot (WB) were used to detect the expression of HER-2 in breast cancer cells (MCF-10A, BT-474 and SK-BR-3). Subsequently, BT-474 cells were treated with different concentrations of pertuzumab (0, 0.1, 0.5, 1, 5, 10 μg/mL), pyrrolizinib (0, 2, 4, 6, 8, 10 nMol/L) or a synergistic mixture of pertuzumab and pyrrolizinib. The cell viability, migration, invasion and programmed cell death were detected by CCK-8, cell colony formation, wound healing, transwell migration, TUNEL apoptosis assay and WB. KEGG pathway analysis was used to identify key pathways with HER-2 involvement. String database was used to analyze the relationship between HER-2 and PI3K/AKT signaling pathway related proteins. Subsequently, the effects of HER-2 knockdown on PI3K/AKT signaling pathway and cell function were investigated.
Results: Elevated HER-2 expression was observed in breast cancer tissues and cells. The combination of pertuzumab and pyrrolitinib effectively reduced HER-2 levels, inhibited cell viability, proliferation, migration and infiltration, and promoted apoptosis. Knockdown of HER-2 inhibited the viability, proliferation, migration and invasion, downregulated the expression of PI3K and AKT, and increased the apoptosis of BT-474 cells, with these effects restored by IGF-1.
Conclusion: Pertuzumab and pyrrolizinib target HER-2 to downregulate the PI3K/AKT signaling pathway, thereby inhibiting breast cancer cells.
期刊介绍：
The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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