METHODS: To investigate the molecular mechanism of action of an endosomal recycling inhibitor (ERI) called primaquine, we performed a reverse-phase protein array (RPPA) assay using a HER2-positive breast cancer cell line. The RPPA findings were confirmed by Western blot and RT-qPCR in several BC cell lines. Novel drug combinations were tested by MTT cell viability and clonogenic assays.
RESULTS: Among the signalling molecules downregulated by ERIs were estrogen receptor-alpha (ER-α) and androgen receptor. We confirmed this finding in other breast cancer cell lines and show that downregulation occurs at the transcriptional level. We also found that ERIs synergise with tamoxifen, a standard-of-care therapy for breast cancer.
CONCLUSIONS: Our data suggest that combining ERIs with hormone receptor antagonists may enhance their efficacy and reduce the emergence of drug resistance.
方法:为了研究称为伯氨喹的内体再循环抑制剂(ERI)的分子机制,我们使用HER2阳性乳腺癌细胞系进行了反相蛋白阵列(RPPA)检测.通过Western印迹和RT-qPCR在几种BC细胞系中证实了RPPA的发现。通过MTT细胞活力和克隆形成测定来测试新的药物组合。
结果:被ERIs下调的信号分子是雌激素受体α(ER-α)和雄激素受体。我们在其他乳腺癌细胞系中证实了这一发现,并表明下调发生在转录水平。我们还发现ERI与他莫昔芬协同作用,乳腺癌的标准治疗方法。
结论:我们的数据表明,将ERIs与激素受体拮抗剂联合使用可以增强其疗效并减少耐药性的出现。