未经证实:天然存在的膳食植物药具有经过时间考验的安全性和抗癌功效,某些化合物的组合已显示出克服难以捉摸的化疗耐药性,这对于提高结直肠癌(CRC)患者的死亡率具有重要意义。因此,在这里,我们假设小檗碱(BBR)和寡聚原花青素(OPCs)可能协同调节多个致癌途径,从而在CRC中发挥优异的抗癌活性.
未经评估:我们进行了一系列细胞培养研究,然后对患者来源的类器官进行询问,以评估BBR和OPC对CRC的协同作用。此外,通过进行全基因组转录组分析,我们确定了联合治疗调节的关键靶基因和通路。
UNASSIGNED:我们首先证明了OPCs通过测量单独或其组合处理的细胞中BBR的荧光信号来促进CRC细胞中BBR的细胞摄取增强。研究了BBR和OPCs对细胞活力的抗肿瘤作用。克隆性,迁移,和入侵。此外,联合治疗在膜联蛋白V结合测定中增强了细胞凋亡。转录组学分析鉴定PI3K-AKT信号通路中的癌基因MYB可能与联合治疗的抗肿瘤特性密切相关。最后,我们在患者来源的CRC肿瘤类器官中成功验证了这些发现.
未经批准:集体,我们首次证明,BBR和OPCs的联合治疗可能通过调节PI3K-Akt信号通路中的细胞凋亡和癌基因MYB协同促进CRC的抗肿瘤特性。
UNASSIGNED: Naturally occurring dietary botanicals offer time-tested safety and anti-cancer efficacy, and a combination of certain compounds has shown to overcome the elusive chemotherapeutic resistance, which is of great significance for improving the mortality of patients with colorectal cancer (CRC). Accordingly, herein, we hypothesized that berberine (BBR) and oligomeric proanthocyanidins (OPCs) might regulate synergistically multiple oncogenic pathways to exert a superior anti-cancer activity in CRC.
UNASSIGNED: We performed a series of cell culture studies, followed by their interrogation in patient-derived organoids to evaluate the synergistic effect of BBR and OPCs against CRC. In addition, by performing whole genome transcriptomic profiling we identified the key targeted genes and pathways regulated by the combined treatment.
UNASSIGNED: We first demonstrated that OPCs facilitated enhanced cellular uptake of BBR in CRC cells by measuring the fluorescent signal of BBR in cells treated individually or their combination. The synergism between BBR and OPCs were investigated in terms of their anti-tumorigenic effect on cell viability, clonogenicity, migration, and invasion. Furthermore, the combination treatment potentiated the cellular apoptosis in an Annexin V binding assay. Transcriptomic profiling identified oncogene MYB in PI3K-AKT signaling pathway might be critically involved in the anti-tumorigenic properties of the combined treatment. Finally, we successfully validated these findings in patient-derived CRC tumor organoids.
UNASSIGNED: Collectively, we for the first time demonstrate that a combined treatment of BBR and OPCs synergistically promote the anti-tumorigenic properties in CRC possibly through the regulation of cellular apoptosis and oncogene MYB in the PI3K-Akt signaling pathway.