关键词: 髓源抑制性细胞, 靶向药物, 卡博替尼, 克唑替尼, AZD9291

Abstract: Objective To investigate the effects of Cabozantinib, Crizotinib and AZD9291 on the percentage of subsets, apoptosis and proliferation of myeloid-derived suppressor cells (MDSCs) from normal mouse bone marrow and spleen. Methods Bone marrow G-MDSCs and M-MDSCs of BALB/c mouse were isolated by immunomagnetic beads and co-cultured with different dosages of Cabozantinib, Crizotinib and AZD9291 for 24 h. The effects of three targeted drugs on MDSCs subtypes were detected by flow cytometry (FCM), the proliferation of MDSCs was detected by CCK-8; The apoptosis of Gr-1+CD11b+ cells was detected by flow cytometry. Results We found that percentage of spleen G(granulocytic) -MDSCs was significantly decreased after treated with Cabozantinib; the percentage of bone marrow G-MDSCs and M(monocytic)-MDSCs was decreased after treated with Crizotinib; Early apoptosis rate of bone marrow MDSCs was increased after treated with Cabozantinib and Crizotinib. There was no obvious change for cell apoptosis after treated with AZD9291. Conclusions Cabozantinib and Crizotinib may reduce the percentage of MDSCs by inducing apoptosis of MDSCs.

Key words: Myeloid derived suppressor cells, Targeted drug, Cabozantinib, Crizotinib, AZD9291