膀胱癌中巨噬细胞浸润与膀胱癌化疗耐药的研究

Effect of macrophage infiltration on chemotherapy resistance of bladder cancer

摘要:

目的 探究膀胱癌分泌趋化因子生长调节基因5（CXCL5）招募巨噬细胞对膀胱癌化疗耐药的影响。 方法 应用Transwell 小室招募实验检测不同处理条件下对人急性单核细胞白血病细胞系（THP-1）招募能力 改变；使用Western blot 测定CXCL5、PARP/cleaved-PARP 蛋白水平改变；通过qRT-PCR 检测CXCL5 的mRNA 水平改变；使用MTT 实验测定巨噬细胞及多柔比星处理对膀胱癌增殖能力的影响。结果 膀胱癌 细胞相对正常膀胱上皮细胞招募更多的THP-1（P <0.05）；膀胱癌细胞相对正常膀胱上皮细胞CXCL5 在蛋 白水平和mRNA 水平表达上调（P <0.05）；膀胱癌细胞中CXCL5 敲减能抑制膀胱癌细胞对THP-1 细胞的 招募能力（P <0.05）；巨噬细胞与膀胱癌细胞共培养后再加入多柔比星cleaved-PARP 上调减弱，细胞存活率 增加（P <0.05）。结论 膀胱癌细胞能分泌CXCL5 招募过多的巨噬细胞促进膀胱癌化疗耐药。

Abstract:

Objective To investigate the effect of macrophage infiltration on chemotherapy resistance of bladder cancer and potential mechanisms. Methods Macrophage recruitment rate was assessed with Transwell chamber. The protein level of CXCL5 and PARP/cleaved-PARP were measured by Western-blot or qRT-PCR. Proliferation rate of macrophage and bladder cancer cells induced by Doxorubicin were detected by MTT assay. Results Bladder cancer cells recruited more THP-1 than normal bladder epithelial cells did (P < 0.05). The protein and mRNA level of CXCL5 in bladder cancer cells were increased significantly compared with normal bladder epithelial cells. The recruitment ability of bladder cancer cells was downregulated greatly with CXCL5 knockdown. After co-cultured with macrophage, the apoptosis rate of bladder cancer cells was suppressed by Doxorubicin. Conclusions Bladder cancer cells recruit macrophages by secreting CXCL5, which assists development of chemotherapy-resistance of bladder cancer.