Cisplatin promotes heart failure in bladder cancer mice by impairing granulocytic myeloid-derived suppressor cells / 上海交通大学学报（医学版）

ABSTRACT

Objective: To investigate the effect of cisplatin on heart failure in bladder cancer mice by impairing granulocytic myeloid-derived suppressor cells (G-MDSCs). Methods: Fifty 8-week-old specific pathogen free (SPF) C3H/He healthy female mice were used to establish the bladder cancer model after subcutaneous injection of MBT-2 mice bladder cancer cells. The mice were divided into group A-E,10 mice in each group,and the group A was set as the blank control group. The group B-E mice were continuously intraperitoneally injected with 5 mg/ (kg•d) isoproterenol for 14 d to successfully establish the heart failure model. The group B was set as the control group. The mice were intraperitoneally injected with 7.5 mg/kg cisplatin every 48 h for chemotherapy,and killed at 14 d in the group C. G-MDSCs were identified,isolated and purified by flow cytometry. 1×107 purified G-MDSCs were intravenously injected into the group D mice via the tail vein every 7 d. The group E mice was treated by combining the procedure of the group C and the group D. The myocardial tissue of the mice was stained by hematoxylin-eosin staining. And the heart failure degree of the mice was analyzed by the heart weight/body weight ratio and the observation under the inverted phase contrast microscope. Results: Flow cytometry results showed that compared with the group B,the level of G-MDSCs in the circulation system of the group C mice was significantly decreased (P=0.000). Hematoxylin-eosin staining and Image J software analysis showed that compared with the group B,the heart weight/body weight ratio and the area of myocardial cells of the group C mice were significantly increased (P=0.001,P=0.002). However,after G-MDSCs injection,the above two indexes in the group D mice were decreased compared with those in the group B (P=0.000,P=0.011). After cisplatin/G-MDSCs combined treatment,the above two indexes in the group E were also decreased compared with those in the group C (P=0.000,P=0.001). Conclusion: G-MDSCs have cardioprotective effects,while cisplatin can facilitate heart failure by impairing G-MDSCs.