三阴性乳腺癌免疫治疗中咖啡酸苯乙酯增效作用探讨

Synergistic effect of caffeic acid phenethyl ester in immunotherapy of triple negative breast cancer

目的 探讨咖啡酸苯乙酯(CAPE)联合程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)抑制剂对三阴性乳腺癌(TNBC)MDA-MB-231细胞增殖、迁移及侵袭的影响。方法 取对数生长期MDA-MB-231细胞分为对照组、PD-1/PD-L1抑制剂组、CAPE组、联合组,分别用MTT、Transwell实验检测以上4组细胞增殖、侵袭和迁移能力。结果 MTT实验结果显示,PD-1/PD-L1抑制剂(F=133.628,P<0.001)、CAPE(F=133.629,P<0.001)对MDA-MB-231细胞增殖抑制作用均呈浓度依赖性。PD-1/PD-L1抑制剂和CAPE半数抑制浓度分别为10.38和13.64 mg/L。对照组、PD-1/PD-L1抑制剂组、CAPE组和联合组D值分别为0.63±0.01、0.39±0.02、0.56±0.01和0.26±0.03,PD-1/PD-L1抑制剂与CAPE两种药物处理MDA-MB-231细胞存在协同作用,F=5.787,P=0.043。对照组、PD-1/PD-L1抑制剂组、CAPE组和联合组细胞迁移数分别为(954.67±27.74)、(601.33±7.08)、(656.92±3.91)和(202.42±31.00)个,PD-1/PD-L1抑制剂与CAPE同时处理MDA-MB-231细胞存在协同作用,F=106.032,P=0.003。对照组、PD-1/PD-L1抑制剂组、CAPE组和联合组侵袭细胞数分别为(842.67±16.04)、(495.75±6.88)、(586.17±8.26)和(116.00±7.55)个,PD-1/PD-L1抑制剂与CAPE同时处理MDA-MB-231细胞存在协同作用,F=17.096,P<0.001。结论 CAPE能增加MDA-MB-231对PD-1/PD-L1抑制剂的敏感性,CAPE在PD-L1免疫靶向治疗乳腺癌中可能具有协同作用。

Objective To investigate the effects of caffeic acid phenethyl ester(CAPE) combined with programmed death factor 1(PD-1)/programmed death ligand 1(PD-L1) inhibitor on the proliferation, migration and invasion of triple negative breast cancer(TNBC) MDA-MB-231 cells.Methods The logarithmic long term MDA-MB-231 cells were divided into control group, PD-1/PD-L1 inhibitor group, CAPE group and combination group.The proliferation, invasion and migration ability of the above four groups were detected by MTT and Transwell test respectively.Results MTT test showed that PD-1/PD-L1 inhibitor(F=133.628,P<0.001) and CAPE(F=133.629,P<0.001) inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner.The IC50of PD-1/PD-L1 inhibitor and CAPE were 10.38 and 13.64 mg/L,respectively.The D values of control group, PD-1/PD-L1 inhibitor group, CAPE group and combination group were 0.63±0.01,0.39±0.02,0.56±0.01 and 0.26±0.03,respectively.There was synergistic effect between PD-1/PD-L1 inhibitor and CAPE in treating MDA-MB-231 cells, F=5.787,P=0.043.The number of cell migration in control group, PD-1/PD-L1 inhibitor group, CAPE group and combination group was 954.67±27.74,601.33±7.08,656.92±3.91 and 202.42±31.00,respectively.PD-1/PD-L1 inhibitor and CAPE simultaneously treated MDA-MB-231 cells had synergistic effect, F=106.032,P=0.003.The number of invasive cells in control group, PD-1/PD-L1 inhibitor group, CAPE group and combination group was 842.67±16.04,495.75±6.88,586.17±8.26 and 116.00±7.55,respectively.PD-1/PD-L1 inhibitor and CAPE simultaneously treated MDA-MB-231cells had synergistic effect,F =17.096,P<0.001.Conclusion CAPE can increase the sensitivity of MDA-MB-231to PD-1/PD-L1inhibitor,and CAPE may play a synergistic role in PD-L1immunotargeting therapy for breast cancer.