Novel FOXM1 Inhibitor STL001 sensitizes different human cancers to broad spectrum of anticancer drugs

We sought to investigate the anticancer effects of the novel FOXM1 inhibitor, STL001 in a variety of human cancers from solid tumors including ovarian cancer, colorectal cancer, breast cancer, and prostate cancers. Here, the capacity of the novel compounds STL001 as FOXM1 inhibitor was verified in human cancer cell lines from solid tumors. Further, we showed here that FOXM1 inhibitor STL001 treatment resulted in sensitization of cancer cells to apoptotic death by multiple chemotherapeutic agents. STL001 was studied further to verify its direct target engagement with FOXM1. We have also provided Transcriptome-supported evidence that STL001 exhibits selectivity toward suppressing FOXM1-controlled regulatory pathways. This study verify and characterize a novel FOXM1 inhibitor STL001 that effectively antagonize FOXM1 activity and sensitize a variety of human cancer cells to traditionally used chemotherapy agents, and may be suitable for further clinical evaluation in targeting chemotherapy resistance human cancers. RNA-seq of FLO-1 and OVCAR-8 cancel cell lines with and without STL001 treatment.

本研究旨在探究新型叉头框蛋白M1（FOXM1）抑制剂STL001对多种实体瘤来源人类癌症的抗肿瘤作用，所涉瘤种包括卵巢癌、结直肠癌、乳腺癌与前列腺癌。本研究首先在实体瘤来源的人类癌细胞系中，验证了新型化合物STL001作为FOXM1抑制剂的活性。进一步研究表明，FOXM1抑制剂STL001可使癌细胞对多种化疗药物诱导的凋亡死亡增敏。本研究还针对STL001与FOXM1的直接靶向结合作用进行了验证实验，并提供了转录组学（Transcriptome）证据，证明STL001可选择性抑制FOXM1调控的信号通路。本研究验证并表征了新型FOXM1抑制剂STL001：该化合物可有效拮抗FOXM1活性，使多种人类癌细胞对临床常用化疗药物增敏，有望在化疗耐药人类癌症的靶向治疗中开展进一步临床评估。本数据集包含经STL001处理与未处理的FLO-1及OVCAR-8癌细胞系的RNA测序（RNA-seq）数据。