Study on Mitochondrial Targeted Drugs Combined with Chloroquine to Overcome Multidrug Resistance in Cancer

OBJECTIVE To study the reversal effect of mitochondrial targeting drug triphenylphosphine-doxorobicin (TPP-DOX) combined with autophagy inhibitor chloroquine on drug resistance of K562/ADR cells in chronic leukemia. METHODS Mitochondrion targeting drug TPP-DOX was prepared. Then CCK8 method was used to measure cell cytotoxicity of K562/DOX after the treatment of TPP-DOX, DOX and their chloroquine combinations. Cell uptake and cell cycle arrest of TPP-DOX, DOX and their chloroquine combination were measured through flow cytometer. The expression of caspase-3 and caspase-9 were examined by using a colorimetric method. RESULTS TPP-DOX combined with chloroquine significantly reversed the drug resistance of K562/DOX cell, and increased the expression of caspase-3 and caspase-9. TPP-DOX couldn't cause cell cycle arrest, indicating that TPP-DOX did not play a role through nuclear entry. CONCLUSION TPP-DOX and chloroquine successfully overcame the drug resistance of K562/DOX.