Paclitaxel is a widely used
chemotherapy drug, but development of resistance leads to treatment failure.
Tumor cells that are treated with a sublethal dose of
paclitaxel for a long period of time show the epithelial-mesenchymal transition (EMT) phenotype, which leads to
metastasis and resistance.
All-trans retinoic acid (ATRA) is always used in combination with
paclitaxel and can reverse EMT in many types of
cancer cells. The ability of ATRA to reverse EMT in chemoresistant cells is still unknown. In the present study, the ability of ATRA to reverse EMT in
paclitaxel-resistant cells was investigated. Three
colorectal cancer cell lines, HCT116, LoVo and CT26, were treated with sublethal doses of
paclitaxel to create resistant cell lines. Western blotting, immunocytochemistry, and "parachute"
dye-coupling assays showed that ATRA reverses EMT, inhibits
nuclear factor kappa B (NF-κΒ), and upregulates gap junctions in
paclitaxel-resistant cells. Scratch wound-healing and Transwell assays showed that ATRA decreases the migration and invasion abilities of
paclitaxel-resistant cells. In addition, the CT26 cell line was used in the Balb/c pulmonary
metastasis model to show that ATRA reduces
metastasis of
paclitaxel-resistant cells in vivo. Given these data, ATRA may reverse EMT by inhibiting NF-κΒ and upregulating gap junctions in
paclitaxel-resistant cells.