Freeze-dried curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles restrain colorectal cancer progression by targeting the notch pathway to regulate epithelial-mesenchymal transition

Abstract

Despite advances in technology and treatment, colorectal cancer (CRC) remains a primary cause of cancer death worldwide, causing nearly 694,000 deaths annually with a high mortality among metastatic cases. Therefore, there is urgency to develop effective strategies to control metastasis or restrain its initiating stage and epithelial-mesenchymal transition (EMT). Activation of Notch1 is noted to positively induce cancer cell growth when inducing EMT. Curcumin is a polyphenol with anticancer activity, which works by activating various molecular pathways in cancer cells. Herein, we established curcumin-Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Cur-NPs) and investigated their physicochemical properties in CRC to provide a novel insight into treatment of CRC. Cur-NPs were established by emulsion solvent evaporation. CRC cells (HCT116, HT29) were co-cultured with 0, 1, 2.5, 5, and 10 μM Cur-NPs, respectively. After treatment, clone formation assay determined CRC cell viability, migration and invasion, whilst Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assessed cell apoptosis. Besides, EMT markers levels in each group were detected to evaluate the impact of Cur-NPs on the EMT process. The transmission electron microscopy (TEM) pictures depicted classical features of Cur-NPs, with encapsulation efficiency of Cur-NPs 70.685±2.597%, and drug loading rate of 2.831±0.108%. The CRC cells absorbed the Cur-NPs within 30 min, and the absorption was as early as 10 min, while fluorescence reached climax at 30 min. The advent of Cur-NPs at different concentration greatly suppressed CRC cell viability and hindered their clone formation in HCT116 and HT29 cells, but elevated apoptotic rate of cancer cells with concentration of Cur-NPs proportional to the rate, while the apoptosis of normal colorectal epithelial cells was not affected. 10 μM Cur-NPs group had the highest apoptosis rate and poorest invasion and migration ability. Moreover, upon treatment with Cur-NPs, E-cadherin expression increased, but the proteins in the Notch pathway declined dramatically. Cur-NPs suppressed CRC cell progression through regulating the Notch signaling pathway and decelerating the EMT process of CRC cells.