机构：[1]Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu Province221002, People’s Republic of China[2]Center of Clinical Oncology, AffiliatedHospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002,People’s Republic of China[3]Department of Cancer Biotherapy Center, ThirdAffiliated Hospital of Kunming Medical University, Kunming, Yunnan Province650118, People’s Republic of China
Tumor targeting small molecular inhibitors are the most popular treatments for many malignant diseases, including cancer. However, the lower clinical response and drug resistance still limit their clinical efficacies. HGFK1, the first kringle domain of hepatocyte growth factor, has been defined as a potent anti-angiogenic factor. Here, we aimed to develop and identify novel nanoparticles-PH1/pHGFK1 as potential therapeutic agents for the treatment of renal cell carcinoma (RCC).We produced a novel cationic polymer-PH1 and investigated the anti-tumor activity of PH1/pHGFK1 nanoparticle alone and its combination therapy with sorafenib in RCC cell line xenografted mice model. Then, we figured out its molecular mechanisms in human RCC cell lines in vitro.We firstly demonstrated that intravenous injection of PH1/pHGFK1 nanoparticles significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice, as well as synergistically enhanced anti-tumor activities of sorafenib. Furthermore, we elucidated that recombinant HGFK1 improved sorafenib-induced cell apoptosis and arrested cell cycle. In addition, HGFK1 could also decrease sorafenib-induced autophagy and stemness via blockading NF-κB signaling pathway in RCC both in vitro and in vivo.HGFK1 could inhibit tumor growth, synergistically enhance anti-tumor activities of sorafenib and reverse its drug resistance evolution in RCC. Our results provide rational basis for clinical application of sorafenib and HGFK1 combination therapy in RCC patients.
基金：
e National Natural Science Foundation of
China (Grant No. 81502221, 81673008), the China Postdoctoral Science
Foundation (Grant No. 2016 M590504), and the Natural Science Foundation
of Jiangsu Province (Grant No. BK20150216), the Jiangsu Province Postdoctoral
Science Foundation (Grant No. 1501088B), the Social development project of
Jiangsu Province (Grant No: BE2017642), the Science and Technology Plan
Projects of Xuzhou (Grant No: KC17012), and the Research Foundation of
Xuzhou Medical University (Grant No. D2015009), Jiangsu Provincial Key Medical
Discipline, the Project of Invigorating Health Care through Science, Technology
and Education (No. ZDXKA2016014), and the International Co-operation Project
In Science & Technology of Yunnan Province (2017IB005).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区医学
小类|2 区肿瘤学
最新[2025]版：
大类|1 区医学
小类|1 区肿瘤学
第一作者：
第一作者机构：[1]Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu Province221002, People’s Republic of China[2]Center of Clinical Oncology, AffiliatedHospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002,People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu Province221002, People’s Republic of China[2]Center of Clinical Oncology, AffiliatedHospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002,People’s Republic of China[3]Department of Cancer Biotherapy Center, ThirdAffiliated Hospital of Kunming Medical University, Kunming, Yunnan Province650118, People’s Republic of China
推荐引用方式(GB/T 7714)：
Gao Xiaoge,Jiang Pin,Zhang Qian,et al.Peglated-H1/pHGFK1 nanoparticles enhance anti-tumor effects of sorafenib by inhibition of drug-induced autophagy and stemness in renal cell carcinoma[J].Journal of experimental & clinical cancer research : CR.2019,38(1):362.doi:10.1186/s13046-019-1348-z.
APA：
Gao Xiaoge,Jiang Pin,Zhang Qian,Liu Qian,Jiang Shuangshuang...&Yao Hong.(2019).Peglated-H1/pHGFK1 nanoparticles enhance anti-tumor effects of sorafenib by inhibition of drug-induced autophagy and stemness in renal cell carcinoma.Journal of experimental & clinical cancer research : CR,38,(1)
MLA：
Gao Xiaoge,et al."Peglated-H1/pHGFK1 nanoparticles enhance anti-tumor effects of sorafenib by inhibition of drug-induced autophagy and stemness in renal cell carcinoma".Journal of experimental & clinical cancer research : CR 38..1(2019):362
医学