Tubeimoside-I (TBM) 通过增加活性氧 (ROS) 的产生来促进各种癌细胞死亡。然而，TBM的具体分子机制及其对奥沙利铂介导的抗CRC活性的影响尚不完全清楚。旨在阐明TBM对奥沙利铂介导的抗CRC活性的治疗效果和潜在分子机制。3-(4,通过 5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物 (MTT)、集落形成、伤口愈合测定和流式细胞术来研究细胞表型和 ROS 生成的变化。采用实时定量PCR（qRT-PCR）和蛋白质印迹法检测相关mRNA和蛋白的表达。最后，小鼠异种移植模型证明了TBM和奥沙利铂联合治疗具有协同抗肿瘤作用。TBM参与ROS介导的内质网（ER）调节协同增强奥沙利铂对结肠癌细胞的抗肿瘤作用应激、C-jun 氨基末端激酶 (JNK) 和 p38 MAPK 信号通路。从机制上讲，TBM 通过抑制热休克蛋白 60 (HSPD1) 的表达来增加结肠癌细胞中 ROS 的产生。敲除 HSPD1 会增加 TBM 诱导的结肠癌细胞抗肿瘤活性和 ROS 生成。小鼠异种移植肿瘤模型进一步验证了联合疗法比单独疗法表现出更强的抗肿瘤作用。TBM和奥沙利铂联合疗法可能是某些CRC患者的有效治疗策略。版权所有©2024。由Elsevier B.V.出版。

Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood.To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin.The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone.Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.Copyright © 2024. Published by Elsevier B.V.