Anti-tumor effect of pcDNA3.1(-)/rMETase-shUCA1 hyaluronic acid-modified G5 polyamidoamine nanoparticles on gastric cancer

Abstract

Background: Recently, recombinant methioninase (rMETase) has been widely exploited as a chemotherapeutic option during gastric cancer treatment. The present study utilized the pcDNA3.1(-)/rMETase-shUCA1 complex and hyaluronic acid (HA)–modified fifth-generation polyamidoamine nanoparticles to evaluate the anti-tumor function of the nanocarrier in Gastric cancer (GC) cells.

Methods: The characteristics of nanoparticles were analyzed using transmission electron microscopy. The GC cell viability and invasion were tested using the CCK-8 assay and the cell invasion assay. The expressions of CD44 phosphorylated mammalian target of rapamycin (p-mTOR), and c-caspase 3 were measured by Western blot assay. Also, a nude mice xenograft model was established to assess the function of HA-polyamidoamineAu-METase-shUCA1 in GC tumor growth.

Results: The transfection of rMETase, alone and in combination with shUCA1 carried by HA-polyamidoamineAu, inhibited GC cell viability, invasion, and tumorsphere formation, and enhanced METase activity. Moreover, HA-polyamidoamine-Au-METase-shUCA1 decreased p-mTOR expression and increased c-caspase 3, while this effect could be reversed by mTOR activator MHY 1485. The CD44 positive cell number and the tumor volume in nude mice, injected with HA-polyamidoamine-Au-METase-shUCA1were reduced.

Conclusion: The HA-polyamidoamine-Au-METase-shUCA1 nanoparticles restrained GC tumor growth, which was partly via the mTOR pathway.

Keywords: Nanoparticles, gastric cancer, UCA1, rMETase