Background
Pancreatic cancer has a high malignancy and rapid progression. It is very easy to metastasize in clinical cases. In recent years, molecular targeted therapy has made some progress in the treatment of some tumors. In this study, we explored the application of miR-25-3p in targeted therapy of pancreatic cancer to improve the survival time of patients with this treatment in the future.
Methods
qRT‒PCR, scratch healing experiments and transwell experiments were applied in this study. iRGD peptide-modified exosomes carrying anti-miR-25-3p and in situ model mice were constructed. The HEK-293T cell line overexpressing the CD63-iRGD-3×FLAG fusion protein and overexpressing the miR-25-3p antisense sequence was obtained by fluorescence sorting using flow cytometry, and exosomes in the culture supernatant of this cell line were obtained by ultracentrifugation. Treatment of pancreatic cancer was simulated by regular tail vein injections of BALB/c nu mice overexpressing CD63-iRGD-3×FLAG fusion protein and loaded with miR-25-3p antisense sequence. The liver and spleen of the mice were stained with HE after a certain course of treatment, and the effect of treatment with exosomes overexpressing CD63-iRGD-3×FLAG fusion protein and loaded with miR-25-3p antisense sequence on liver metastasis of pancreatic cancer was observed.
Results
There was a positive correlation between miR-25-3p and the invasive migration ability of pancreatic cancer cell lines in the Panc-1 and Panc-3 cell lines, and the invasive migration ability of pancreatic cancer was enhanced by overexpression of miR-25-3p (P < 0.05). Treatment with exosomes overexpressing the CD63-iRGD-3×FLAG fusion protein and loaded with the miR-25-3p antisense sequence slowed the weight loss of mice, and pancreatic cancer cell lines showed specific high uptake of such exosomes in mice. Treatment with exosomes overexpressing the CD63-iRGD-3×FLAG fusion protein loaded with the miR-25-3p antisense sequence significantly inhibited liver metastasis and spleen metastasis of pancreatic cancer in mice.
Conclusion
Exosomes overexpressing the CD63-iRGD-3×FLAG fusion protein and loaded with the miR-25-3p antisense sequence inhibited the invasive migration of pancreatic cancer cell lines both in vivo and ex vivo, which hopefully provides a new idea for molecular targeted therapy in the treatment of pancreatic cancer to improve the quality of life and prolong the survival time of pancreatic cancer patients.