Effects of Recepteur D’origine Nantais/Phosphatidylinositol 3 Kinase Pathway Mediated by Polymer Biodegradable Sustained-Release Materials on Proliferation and Apoptosis of Uterine Fibroids

Abstract

This research was aimed to investigate the effects of biodegradable letrozole (LE) sustained release (SR) polymer material on the biological behavior of uterine fibroids (UFs) and RON/PI3K signaling pathway (SPW). Poloxamer 188 (P188) and poly L lactide acid (PLLA) were selected to prepare the degradable SR electrospinning (ES) materials LE/P188/PlLA-1 (LE concentration: 6.25%), LE/P188/PLLA-2 (LE concentration: 12.25%), and LE/P188/PLLA-3 (LE concentration: 25%) with different concentrations of LE. UF cells were then co-cultured with free LE and degradable SR ES materials. Cell proliferation and apoptosis were detected by MTT and flow cytometry, respectively. The expression changes of apoptosis-related proteins (Bcl-2, Bax, and caspase-3), epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, Vimentin), and RON/PI3K SPW-related proteins (RON and PI3K) were detected by western blot. The average diameter of LE/P188/PLLA-1, LE/P188/PLLA-2, and LE/P188/PLLA-3 were (145.6±20.8) nm, (158.1±16.3) nm, and (173.4±20.1) nm, respectively. Moreover, it possessed the obvious characteristics of LE, P188, and PLLA. LE/P188/PLLA-3 had the lowest SR rate of LE but the longest SR duration. Compared with normal cells, the proliferation inhibition rate (PIR) and apoptosis rate (AR) of LE and its degradable SR ES materials were increased (P <0.05). While expressions of Bax, caspase-3, E-cadherin, and PI3K were increased, Bcl-2, N-cadherin, Vimentin, and RON were decreased (P <0.05). In contrast to the free LE, the cell proliferation inhibition rate (PIR) and apoptosis promotion rate (APR) of LE degradable SR ES materials were increased, the levels of Bax, caspase-3, E-cadherin, and PI3K were increased, and the levels of Bcl-2, N-cadherin, Vimentin, and RON were decreased (P <0.05). The results herein were concentration-dependent. The preparation of LE degradable SR ES materials with P188/PLLA can improve the therapeutic effect of LE. LE degradable SR ES materials can effectively inhibit the proliferation of UFs, promote cell apoptosis, inhibit its EMT process and activation of RON/PI3K SPW in a concentration-dependent manner.