DOPAMINE ACTIVATES ACUTE MYELOID LEUKAEMIA NLRP3 INFLAMMASOME THROUGH THE DR5 RECEPTOR PATHWAY TO PROMOTE CANCER AND INDUCE CHEMOTHERAPY RESISTANCE

Huifang Ma^*

Department of laboratory, Heji Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi Province, China

Objective: To explore the role and mechanism of dopamine (DA)-activating acute myeloid leukaemia (AML) NOD-like receptor family pyrin domain (NLRP3) inflammasomes on tumour progression and chemotherapy resistance through the dopamine receptor 5 (DR5) pathway. 

Methods: AML cell line U937 was divided into a control group, DA group, SKF82958 group and chlorprothixene group. The control group was treated with 1μL/mL DMSO, the DA group was treated with 50μmol/L DA, the SKF82958 group was treated with DR1/5 agonist SKF82958 and the chlorprothixene group was treated with 50 μmol/L DA. Moreover, 30 minutes before DA treatment, 36 nmol/L of the DR1/5 antagonist chlorprothixene was used for intervention. Proliferation and cleaved caspase-1, IL-1β protein expression levels and IL-1β levels were compared at 24, 48 and 72 h in each group. Then, 30μg/L Adriamycin (ADR) was added to each group for 48 h, and the IC50 values of ADR were compared. 

Results: At 24, 48 and 72 h, the proliferation OD values of U937 cells in the DA group and SKF82958 group were significantly higher than those in the control group. The proliferation OD values of U937 cells in the chlorprothixene group were significantly lower than those in the DA group (P<0.05). Expression levels of NLRP3, cleaved caspase-1 and cleaved IL-1β protein in U937 cells in the DA and SKF82958 groups were significantly higher than those in the control group (P<0.05). The expression levels of NLRP3, cleaved caspase-1 and cleaved IL-1β in U937 cells in the chlorprothixene group were significantly lower than those in the DA group (P<0.05). The levels of IL-1β in U937 cells in the DA and SKF82958 groups were significantly higher than those in the control group (P<0.05). The IL-1β level of U937 cells in the chlorprothixene group was significantly lower than that in the DA group (P<0.05). The ADR values of U937 cells in the DA and SKF82958 groups were significantly higher than those in the control group (P<0.05). The ADR and Ara-C IC50 values of U937 cells in the chlorprothixene group were significantly lower than those in the DA group (P<0.05). 

Conclusion: DA can activate the AML NLRP3 inflammasome through the DR5 receptor pathway to promote cancer and induce chemotherapy resistance.