Regional delivery of Nano-taxol achieved more efficient killing of cancer stem cells.
Notes: (A) Representative figures for tumor sphere-forming ability of the treated tumors are shown. The mice were implanted with ES-2 cells (2×106 per mouse) on day 1 and were treated on days 5, 8, and 11 at the indicated doses. The tumors were retrieved on day 14 from the mice in each indicated group. The tumors were dissociated into single-cell suspensions and cultured in an ultra-low attachment dish (Corning 3471) for 10 days. The tumors that received regional delivery of Nano-taxol show almost no microsphere formation, whereas the tumors in the other three treated groups (intravenous Taxol®, intraperitoneal Taxol, intraperitoneal Nano-taxol) show increased microsphere formation compared with the control group. (B) Summary of tumor sphere formation (mean ± standard deviation). (C) Flow cytometry analysis of Hoechst 33342-stained cells and identification of side population cells. The percentages of the side population cells are shown. (D–G) RT-PCR analysis of the expression of a stemness marker (D), genes associated with EMT and expression of an epithelial or mesenchymal phenotype (E), genes associated with tumor angiogenesis (F), and genes associated with multidrug resistance (G). (H) CXCR4-CXCL12 axis in stem cell maintenance. Tumors treated by regional delivery of Nano-taxol showed repressed CXCR4-CXCL12 expression compared with the control group, whereas the tumors in the other three treated groups (intravenous Taxol®, Taxol® IP, Nano-taxol IV) showed increased expression of CXCR4-CXCL12 compared with the control group. The experiments were performed in triplicate. *P<0.05.
Abbreviations:
β-FGF, beta-fibroblast growth factor; E-Cad, E-cadherin; EGF, epidermal growth factor; EMT, epithelial-to-mesenchymal transition; HIF-1α, hypoxia-inducible factor-1 alpha; IL-8, interleukin-8; i.v., intravenous; i.p., intraperitoneal; PDGF-α, platelet-derived growth factor-alpha; PLGF, placental growth factor; VEGF-α, vascular endothelial growth factor-alpha; Vim, vimentin; RT-PCR, Reverse transcription-polymerase chain reaction.