HAL光动力治疗联合吡柔比星对膀胱癌细胞的杀伤作用及其机制的体外实验研究

Killing effect of hematoporphyrin derivative photodynamic therapy combined with pirarubicin on bladder cancer cells and drug resistance in vitro

目的探讨六氨基乙酰丙酸(HAL)光动力治疗(PDT)联合吡柔比星(THP)在体外对膀胱癌细胞的协同杀伤作用及可能的机制。方法将膀胱癌细胞株RT4和T24细胞分为空白对照组、PDT组、THP组、PDT+THP组,各组经过相应的处理后,采用CCK-8法检测对细胞增殖的影响,Western blot检测P-gp蛋白的表达,Hoechst/PI双染法检测对细胞凋亡的影响,RT-q PCR检测Bcl-2和Bax基因的表达。结果与单独PDT处理和单独THP处理相比,PDT+THP处理能够显著抑制RT4和T24细胞的增殖能力(均P<0.01),降低癌细胞P-gp蛋白的表达,并增加细胞凋亡能力、下调Bcl-2基因表达(均P<0.01)、上调Bax基因表达(均P<0.01)。结论HAL介导的PDT联合THP对膀胱癌细胞具有协同杀伤作用,其机制可能与联合治疗降低了癌细胞的耐药性、促进癌细胞凋亡有关。

Objective To explore the synergistic effect and possible mechanism of HAL photodynamic therapy(PDT)combined with pirarubicin(THP)in killing bladder cancer cells in vitro.Methods RT4 and T24 bladder cancer cells were divided into a blank control group,a PDT group,a THP group,and a PDT+THP group.After the corresponding treatment of each group,the effects on cell proliferation were detected by CCK-8,P-gp protein expression by Western blot,apoptosis by Hoechst/PI double-staining,and Bcl-2 and Bax gene expression by RT-qPCR.Result Compared with PDT alone and THP alone,PDT combined with THP significantly inhibited the proliferation ability of RT4 and T24 bladder cancer cells(both P<0.01),decreased the expression of P-gp protein in cancer cells,increased apoptosis,down-regulated Bcl-2 gene expression(both P<0.01),and up-regulated Bax gene expression(both P<0.01)in bladder cancer cells.Conclusions HAL-PDT combined with THP had a synergistic effect on bladder cancer cells,and the mechanism may be related to the fact that the combined therapy reduced the drug resistance of cancer cells and promoted the apoptosis of cancer cells.