A novel nitidine chloride nanoparticle overcomes the stemness of CD133 + EPCAM + Huh7 Hepatocellular Carcinoma Cells for liver cancer therapy

Abstract:

Background: Stemness of CD133⁺EPCAM⁺ hepatocellular carcinoma cells ensures cancer resistance to apoptosis ,which is a challenge to current liver cancer treatments. Here we discovered that a novel nitidine chloride nanoparticle (TPGS-FA/NC, TPGS-FA: folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate , NC: nitidine chloride) targeted Huh7 human hepatocellular carcinoma and promoted its apoptosis in mice and cells. CD133 expression regulates AQP3 expression, promoting to increase the stemness properties of hepatoma cells. Importantly, AQP3 is association with stimulation and nuclear translocation of STAT3 with a increasing expression level of CD133 .

Methods: Cell viability was assessed by MTT and colony assays.TPGS-FA/NC nanoparticles were assayed by using confocal microscopy targeting Huh7 Hepatocellular Carcinoma Cells . A sphere culture technique was used to enrich cancer stem cells (CSC) and sort the CD133⁺EPCAM⁺ Huh 7 cells by magnetic-activated cell sorting assay. The proteins were examined by immunohistochemistry and western blotting assay.

Result: TPGS-FA/NC nanoparticles reduced the CD133⁺EPCAM⁺ Huh7 cells numbers in vitro. Furthermore, its time-dependently suppressed the AQP3/CD133/STAT3/JAK signaling pathways. Nitidine chloride nanoparticles therapy prevented and treated hepatocellular carcinoma in mice without adverse effects.

Conclusions: TPGS-FA/NC is shown to a promising and safe drug against liver cancer therapy via AQP3/STAT3/CD133 axis.