药物科学与新兴药物杂志

A Novel Nitidine Chloride Nanoparticle Inhibits the Stemness of CD133+EPCAM+ Huh7 Hepatocellular Carcinoma Cells

Hua Zhu*, Tong Li, Danni Li, Qiying Zhang, Yuzhu Zhou

Nitidine chloride is a natural product. We synthesized novel nanoparticles of Nitidine chloride (TPGS-FA/NC), which evaluated anti-hepatocellular carcinoma potential capability in vitro and in vivo. Cell viability was assessed by MTT and colony assays; TPGS-FA/NC was examined by Confocal Microscopy though targeting Huh7 Hepatocellular Carcinoma Cells .A sphere culture technique was used to enrich Cancer Stem Cells (CSC) in Huh7 cells. The in vivo antitumor efficacy of TPGS-FA/NC was evaluated in Huh7 cell xenograft model, which were administered by TPGS-FA/NC for 2 weeks. TPGSFA/NC (10, 20, 40 μg/mL) dose-dependently inhibited the proliferation of HCC cells. Interestingly, TPGS-FA/NC (10, 20,40 μg/mL) drastically reduced the EpCAM+/CD133+ cell numbers, which suppressed the sphere formation and inhibited the expression of stem cell marker in the Huh7 spheroids. Additionally, TPGS- A/NC time dependently suppressed the AQP3/CD133/STAT3/JAK signaling pathways in Huh7 cells. In Huh7 cells xenograft bearing nude mice, TPGS-FA/NC administration significantly inhibited the tumor growth and markedly reduced the number of cancer stem-like cells in the tumors. TPGS-FA/NC treatment also reduced the expression of stem cell markers. The novel nitidine chloride nanoparticles markedly inhibited the HCC tumor growth through multiple mechanisms, and it may be a potential candidate drug for the
therapy of hepatocellular carcinoma.