The effects of novel chitosan-targeted gemcitabine nanomedicine mediating cisplatin on epithelial mesenchymal transition, invasion and metastasis of pancreatic cancer cells.

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/m2 . 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.