姜黄素联合人类细胞因子诱导的杀伤细胞对卵巢癌细胞增殖的抑制作用及其机制

Inhibitory effects of curcumin associated with CIK cells on proliferation of ovarian carcinoma cells and their mechanisms

目的:观察姜黄素(Cur)联合人类细胞因子诱导的杀伤(CIK)细胞在体外对人卵巢癌浆液性囊腺癌细胞SKOV-3的增殖抑制作用,探讨其协同抗肿瘤作用及其可能机制。方法:诱导脐血CIK细胞,将SKOV-3细胞随机分为Cur组、CIK细胞组和Cur联合CIK细胞组,MTT法测定各组细胞的增殖抑制率,RT-PCR检测各组细胞Fas相关死亡结构蛋白Fas、Fas相关死亡结构蛋白(FADD)和Caspase-3mRNA的表达。结果:与Cur组和CIK细胞组比较,Cur联合CIK细胞组SKOV-3细胞增殖抑制率增大,并且随时间的延长或剂量的增加,增殖抑制率亦增加,在效靶比为12.5∶1,20μmol·L-1 Cur作用48h时,SKOV-3细胞增殖抑制率达到76.2%;Cur联合CIK细胞组与Cur组和CIK细胞组比较,SKOV-3细胞Fas及Caspase-3的mRNA表达水平增加(P<0.05),Cur组、CIK细胞组和Cur联合CIK细胞组SKOV-3细胞FADD-mRNA表达无明显变化。结论:CIK细胞与Cur合用具有协同抗肿瘤作用,其效应可能与促进SKOV-3细胞Fas及Caspase-3的mRNA表达有关。

Objective To observe the inhibitory effects of curcumin（Cur） associated with cytokine-induced killer（CIK） cells on proliferation of ovarian carcinoma SKOV-3 cells in vitro,and discuss whether they have synergetic anti-tumor effects if they are used together and the possible mechanism.Methods The CIK cells were induced from umbilicus cord blood,and the SKOV-3 cells were randomly divided into Cur group,CIK cells group and Cur associated with CIK cells group.The inhibitory rates of proliferation in each group were detected by MTT method.The mRNA levels of Fas,Fas associated death domain protein（FADD） and Caspase-3 in each group were measured by RT-PCR.Results Compared with Cur and CIK cells groups,the inhibitory rate of proliferation of SKOV-3 cells in Cur associated with CKI cells group was increased,and the inhibitory rate was increased with the time prolongation and dose increasing.The inhibitory rate of SKOV-3 cells approached 76.2% when the concentration of effector to target ratio was 12.5∶1 and 20 μmol·L-1 Cur was used for 48 h.The mRNA levels of Fas and Caspase-3 in SKOV-3 cells were increased in Cur associated with CIK cells group compared with Cur and CIK cells groups.The mRNA levels of FADD didn’t have significant changes in various groups.Conclusion The effect of anti-tumor can be enhanced in a synergetic pattern when Cur and CIK cells are used together.Its mechanism may be related with the promoting effects on the mRNA levels of Fas and Caspase-3 in SKOV-3 cells when they are used together.