Research on compound combination of Realgar-Indigo naturalis Formula to reverse APL arsenic resistance by regulating autophagy through mTOR pathway

Abstract

Abstract Background: Acute promyelocytic leukemia (APL) used to be the most fatal type of acute myeloid leukemia (AML). After the emerge of all-trans retinoic acid and arsenic trioxide treatment, the Complete Response (CR) rate could reach 90%. In China, compound Realgar-Indigo naturalis Formula (RIF) are used instead of arsenic trioxide for home therapy. It has the advantages of reduced hospitalization time and more favorable price, and the CR rate is not lower than that of all-trans retinoic acid and arsenic trioxide therapy. However, drug resistances greatly affect the prognosis of patients. Compared with all-trans retinoic acid, previous studies on arsenic resistance are more limited. Methods: In this study, the stable expression of arsenic-resistant cell line HL60-PMLA216V-RARα was established, and the mechanism of RIF reversing APL arsenic resistance was studied. Results and Conclusion: We illustrated that the synergistic effect of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, promote cell differentiation, reduce mitochondrial membrane potential, and degrade arsenic-resistant PMLA216V-RARα.