PMID- 29035831 OWN - NLM STAT- MEDLINE DCOM- 20180726 LR - 20221207 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 96 DP - 2017 Dec TI - The effects of novel chitosan-targeted gemcitabine nanomedicine mediating cisplatin on epithelial mesenchymal transition, invasion and metastasis of pancreatic cancer cells. PG - 650-658 LID - S0753-3322(17)33603-X [pii] LID - 10.1016/j.biopha.2017.10.026 [doi] AB - OBJECTIVE: The study aimed to evaluate the effects involved with the novel chitosan gemcitabine (Gem) nanoparticles mediating cisplatin (DDP) on epithelial mesenchymal transition (EMT), invasion and metastasis of pancreatic cancer (PC) cells. METHODS: A total of 62 healthy purebred BALB/C of specific-pathogen free (SPF) female nude mice were recruited and a SW1990 cell line was subsequently cultured. A heterotopic xenograft tumor model was constructed. After determining the optimal drug concentration, the nude mice were assigned into the control, glycol chitosan (GC)-Gem microsphere, antibody Complex (Abc)-GC-Gem and Abc-GC-Gem microsphere+DDP groups (n=8 in each group). The tumor morphology of the nude mice was observed and HE staining was used to observe the pathological changes of the respective tissues. TUNEL staining was performed to detect cell apoptosis, while immunohistochemistry was employed for analysis of the positive expression rate of EGFR and the number of microvessel density (MVD). Both RT-qPCR and Western blotting were utilized for mRNA and protein expressions of VEGF, EGFR, Bcl-2, Bax, Survivin, Bak, E-cadherin and Vimentin analysis. RESULTS: The optimal drug concentration of Gem was determined to be 120mg/m(2). In comparison to the control group, tumor size, weight, positive expression rate of EGFR and tumor MVD, as well as mRNA and protein expressions of Bax and E-cadherin decreased, while the inhibition rate (IR) and apoptosis index (AI), expression of VEGF, EGFR, Bcl-2, Survivin, Bak and Vimentin increased in the GC-Gem microsphere, Abc-GC-Gem microsphere and Abc-GC-Gem microsphere+DDP groups. Compared with the GC-Gem microsphere group, Abc-GC-Gem and Abc-GC-Gem microsphere+DDP groups had decreases concerning tumor size and weight, positive rate of protein expression of EGFR and tumor MVD, as well as the expression of Bax and E-cadherin, and enhances on IR and AI, expression of VEGF, EGFR, Bcl-2, Survivin, Bak, and Vimentin, which were the most obvious in the Abc-GC-Gem+DDP group (P<0.05). CONCLUSION: Novel Gem nanoparticles aid in mediating DDP to inhibit PC cell invasion and migriation, promote PC cell apoptosis and enhance the efficacy of chemotherapy. Our findings demonstrated that Gem administered in combination with DDP was more effective than Gem alone. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Yu, Haibo AU - Yu H AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Song, Hongliang AU - Song H AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Xiao, Jun AU - Xiao J AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Chen, Haichuan AU - Chen H AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Jin, Xiaodan AU - Jin X AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Lin, Xizhou AU - Lin X AD - Department of Digestive Diseases, Wenzhou People's Hospital, The Third Clinical College of Wenzhou Medical University, Wenzhou 325000, PR China. FAU - Pan, Bujian AU - Pan B AD - Department of Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: panbujianwz@163.com. FAU - Ji, Wu AU - Ji W AD - Research Institute of General Surgery, Nanjing School of Clinical Medicine, Southern Medical University (Nanjing General Hospital of Nanjing Military Region), Nanjing, 210002, PR China. Electronic address: jiwuvip@126.com. LA - eng PT - Journal Article DEP - 20171106 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0W860991D6 (Deoxycytidine) RN - Q20Q21Q62J (Cisplatin) RN - 0 (Gemcitabine) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cisplatin/*administration & dosage MH - Deoxycytidine/administration & dosage/*analogs & derivatives MH - Dose-Response Relationship, Drug MH - Drug Delivery Systems/*methods MH - Epithelial-Mesenchymal Transition/*drug effects/physiology MH - Female MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Nanomedicine/*methods MH - Neoplasm Invasiveness/pathology/prevention & control MH - Pancreatic Neoplasms/*drug therapy/pathology MH - Treatment Outcome MH - Tumor Burden/drug effects/physiology MH - Xenograft Model Antitumor Assays/methods MH - Gemcitabine OTO - NOTNLM OT - DDP OT - Epithelial mesenchymal transition OT - Gemcitabine OT - Invasion OT - Metastasis OT - Nanoparticles OT - Pancreatic cancer EDAT- 2017/10/17 06:00 MHDA- 2018/07/27 06:00 CRDT- 2017/10/17 06:00 PHST- 2017/07/19 00:00 [received] PHST- 2017/09/26 00:00 [revised] PHST- 2017/10/02 00:00 [accepted] PHST- 2017/10/17 06:00 [pubmed] PHST- 2018/07/27 06:00 [medline] PHST- 2017/10/17 06:00 [entrez] AID - S0753-3322(17)33603-X [pii] AID - 10.1016/j.biopha.2017.10.026 [doi] PST - ppublish SO - Biomed Pharmacother. 2017 Dec;96:650-658. doi: 10.1016/j.biopha.2017.10.026. Epub 2017 Nov 6.