机构：[1]State Key Laboratory of Oncogenes andRelated Genes, Shanghai Cancer Institute,Renji Hospital, School of Medicine,Shanghai Jiao Tong University, Shanghai200032, People’s Republic of China[2]Department of Clinical Medicine, NorthSichuan Medical College, Sichuan 637100,People’s Republic of China[3]Departmentof Ultrasound, Shanghai GeneralHospital, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai 200080,People’s Republic of China
Platinum/paclitaxel-based chemotherapy is the strategy for ovarian cancer, but chemoresistance, inherent or acquired, occurs and hinders therapy. Therefore, further understanding of the mechanisms of drug resistance and adoption of novel therapeutic strategies are urgently needed.In this study, we report that sphingosine-1-phosphate receptor-1 (S1PR1)-mediated chemoresistance for ovarian cancer. Then we developed nanoparticles with a hydrophilic PEG2000 chain and a hydrophobic DSPE and biodegradable CaP (calcium ions and phosphate ions) shell with pH sensitivity as a delivery system (CaP-NPs) to carry BAF312, a selective antagonist of S1PR1 (BAF312@CaP-NPs), to overcome the cisplatin (DDP) resistance of the ovarian cancer cell line SKOV3DR.We found that S1PR1 affected acquired chemoresistance in ovarian cancer by increasing the phosphorylated-signal transduction and activators of transcription 3 (P-STAT3) level. The mean size and zeta potential of BAF312@CaP-NPs were 116 ± 4.341 nm and -9.67 ± 0.935 mV, respectively. The incorporation efficiency for BAF312 in the CaP-NPs was 76.1%. The small size of the nanoparticles elevated their enrichment in the tumor, and the degradable CaP shell with smart pH sensitivity of the BAF312@CaP-NPs ensured the release of BAF312 in the acidic tumor niche. BAF312@CaP-NPs caused substantial cytotoxicity in DDP-resistant ovarian cancer cells by downregulating S1PR1 and P-STAT3 levels.We found that BAF312@CaP-NPs act as an effective and selective delivery system for overcoming S1PR1-mediated chemoresistance in ovarian carcinoma by inhibiting S1PR1 and P-STAT3.
基金：
This research was supported by the National Natural Science Foundation of China (No. 81972886, No. 81773272, No.81771839, No. 81671687 and No. 81874479), the State Key Laboratory of Oncogenes and Related Genes (No. 91-17-20), Medical-Engineering Joint Funds from Shanghai Jiao Tong University (No. YG2017QN43), Shanghai Municipal Commission of Health and Family Planning(No. 20174Y0123).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区医学
小类|2 区药学3 区纳米科技
最新[2023]版：
大类|2 区医学
小类|2 区药学3 区纳米科技
第一作者：
第一作者机构：[1]State Key Laboratory of Oncogenes andRelated Genes, Shanghai Cancer Institute,Renji Hospital, School of Medicine,Shanghai Jiao Tong University, Shanghai200032, People’s Republic of China
通讯作者：
通讯机构：[1]State Key Laboratory of Oncogenes andRelated Genes, Shanghai Cancer Institute,Renji Hospital, School of Medicine,Shanghai Jiao Tong University, Shanghai200032, People’s Republic of China[3]Departmentof Ultrasound, Shanghai GeneralHospital, Shanghai Jiao Tong UniversitySchool of Medicine, Shanghai 200080,People’s Republic of China[*1]State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute, Renji Hospital School of Medicine, Shanghai Jiao Tong University, 2200/25 Xietu Road, Shanghai 200032, People’s Republic of China[*2]Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, People’s Republic of China
推荐引用方式(GB/T 7714)：
Ke Gong,Yang Dong,Liting Wang,et al.Nanoparticle BAF312@CaP-NP Overcomes Sphingosine-1-Phosphate Receptor-1-Mediated Chemoresistance Through Inhibiting S1PR1/P-STAT3 Axis in Ovarian Carcinoma.[J].International journal of nanomedicine.2020,15:5561-5571.doi:10.2147/IJN.S248667.
APA：
Ke Gong,Yang Dong,Liting Wang,Yi Duan,Jian Yu...&Yourong Duan.(2020).Nanoparticle BAF312@CaP-NP Overcomes Sphingosine-1-Phosphate Receptor-1-Mediated Chemoresistance Through Inhibiting S1PR1/P-STAT3 Axis in Ovarian Carcinoma..International journal of nanomedicine,15,
MLA：
Ke Gong,et al."Nanoparticle BAF312@CaP-NP Overcomes Sphingosine-1-Phosphate Receptor-1-Mediated Chemoresistance Through Inhibiting S1PR1/P-STAT3 Axis in Ovarian Carcinoma.".International journal of nanomedicine 15.(2020):5561-5571
医学