Mesenchymal stem cell derived exosomes as Nanodrug carrier of doxorubicin combined with PVT1 siRNA inhibits the progression of gastric cancer

Abstract

Background and study aims: Mesenchymal stem cell-derived exosomes (MSC-Exos) have been used as drug delivery vehicles for the treatment of gastric cancer. This study aimed to explore the effects of doxorubicin-loaded exosomes (Exo-Dox) combined with the long noncoding RNA PVT1 on gastric cancer (GC) development.

Material and methods: CCK-8 and immunohistochemistry were used to assess cell proliferation. The morphology and size of the exosomes and Exo-Dox were determined. The distribution of free Exos and Exo-Dox in cells was observed under a fluorescence microscope. Cell migration and invasive ability were assessed using wound healing and Transwell assays. In addition, the protective effects of Exo-Dox were confirmed in a xenograft tumor model.

Results: Exosomes were successfully isolated from MSCs and identified. The size of Exo-Dox was greater than that of free Exos. The acidic environment promoted the release of doxorubicin, and exosomes promoted the cellular uptake of doxorubicin. Compared with doxorubicin alone, Exo-Dox exhibited better antitumor effects on gastric cancer, inhibiting the growth, migration and invasion of gastric cancer cells. Additionally, combined therapy of Exo-Dox with si-PVT1 clearly suppressed the proliferation, migration and invasive ability of gastric cancer cells. Exo-Dox combined with si-PVT1 inhibited tumor growth and metastasis in a xenograft model.

Conclusion: Doxorubicin-loaded exosomes combined with si-PVT1 suppressed the progression of GC.

Keywords: Doxorubicin-loaded exosomes; Gastric cancer; PVT1.