小白菊内酯通过靶向c-myc G-四链体抑制乳腺癌细胞增殖和迁移

Effect of parthenolide on proliferation and migration of MCF-7 breast cancer cells by targeting the c-myc G-quadruplex

探讨小白菊内酯(parthenolide,PTL)通过靶向c-myc基因G-四链体抑制乳腺癌细胞增殖和迁移。采用表面等离子共振法和荧光共振能量转移法研究小白菊内酯与G-四链体的结合能力和热稳定能力;RT-PCR和Western blot实验检测PTL对c-myc蛋白转录和表达水平的影响;MTT和细胞划痕实验检测PTL对MCF-7细胞增殖和迁移的影响。结果表明,PTL对c-myc G-四链体有较好的结合和稳定能力,结合KD为13.1μmol·L-1;对乳腺癌细胞MCF-7作用24、48和72 h的半数抑制浓度分别为21.3、14.5和9.1μmol·L-1;且PTL可以有效抑制MCF-7细胞的迁移。PTL通过靶向c-myc G-四链体抑制肿瘤细胞中c-myc基因的转录和表达,进而抑制乳腺癌细胞增殖和迁移。

This research investigated the effect of parthenolide on the proliferation and migration of human breast cancer cells and explored the molecular mechanism of that effect.Surface plasmon resonance and fluorescence resonance energy transfer melting were used to detect the binding and stabilizing ability of PTL and Gquadruplex.MTT assays were used to determine the effect of PTL on the proliferation of MCF-7 breast cancer cells.A wound healing assay was performed to detect the migration of MCF-7.The results indicate that PTL shows good binding and stabilizing activities with c-myc G-quadruplex with a KD=13.1μmol·L-1.PTL inhibited the proliferation of MCF-7 cells with an IC50 of 21.3μmol·L-1(24 h),14.5μmol·L-1(48 h)and 9.1μmol·L-1(72 h).PTL inhibited MCF-7 breast cancer cell proliferation and migration and down-regulated the transcription and expression level of c-myc by targeting G-quadruplex.