ANTICANCER GENE-ASSOCIATED CATIONIC LIPID AND ESTROGENIC DRUG FORMULATION FOR THE TREATMENT OF AGGRESSIVE PANCREATIC CANCER AND BREAST CANCER STEM CELL

摘要

Herein, we report the development of an anticancer lipid-based formulation that kills very aggressive pancreatic cancer cells and breast cancer stem cell (CSC)-like cells. This formulation is a concoction of an anticancer agent, ESC8 and a glucocorticoid receptor (GR)-targeting cationic lipid delivery system, DX. When complexed with plasmid DNA this formulation in association with the hydrophobic anticancer agent (ESC8) initiates killing of cancer cells and CSC-like cells within 3h. When anticancer gene encoded plasmid is used residual cancer cells were also eradicated after 2 days of exposure. The formulation-free naked ESC8 requires at least ten-fold more concentration and 3 days of continuous treatment to get similar level of killing. The formulation in association with plasmid encoding neuropilin Sh-RNA could inhibit the tumor growth in mice orthotopically implanted with very aggressive mouse breast cancer cell, ANV-1. This cell is known to produce breast CSC- like cells that shows phenotype of advanced cancer relapsing. There is no visible toxic effect of this formulation when injected in mice, indicating that the formulation has minimum to no toxic effect to normal homeostasis. To our knowledge, there is no other evidence of a treatment regimen that kills differentiated cancer cell- originating stem cells. Our discovery is the first of its kind potential therapeutics that not only harness aggressive cancer but also eradicates breast cancer stem cell-like cells.