研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

C188-9 在临床相关的低浓度下可减少患者特异性原发性乳腺癌细胞增殖。

C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

发表日期:2024 Aug 22
作者: Rongji Zheng, Tian Guan, Chaoqun Hong, Yao Yao, Yutong Fang, Wei Huang, Chunfa Chen, Huancheng Zeng, Jiman Huang, Hui Lin, Bingfeng Chen, Rendong Zhang, Dongmei Chen, Zhechun Ding, Haoyu Zeng, Jundong Wu
来源: Journal of Translational Medicine

摘要:

STAT3是乳腺癌癌基因的转录激活因子,这表明它可能是乳腺癌的潜在治疗靶点。因此,本研究通过具有患者特异性原代细胞(PSPC)的新型临床前平台,探讨了STAT3信号通路抑制剂C188-9在乳腺癌治疗中的潜在应用。PSPC是从获得的乳腺癌样本中分离出来的通过来自 15 名患者捐赠者的活检或手术,并得到他们的充分认可。 PSPCs用C188-9或其他化疗剂处理,然后用细胞活力测定进行分析。 Western blot法和实时定量PCR检测相应PSPCs STAT3信号通路的表达和活性。正常(实验)浓度的C188-9处理对PSPCs增殖具有有效的抑制作用。同时,与一些其他传统化疗药物相比,长时间使用低(临床相关)浓度的 C188-9 治疗会降低 PSPC 的细胞活力。此外,C188-9 降低了部分而非所有患者样本的 PSPC 中 pSTAT3 的表达水平。 C188-9 的治疗通过抑制 STAT3 至 C-myc 信号通路来降低乳腺癌样本的细胞活力。在这项研究中,我们测试了一种低临床相关浓度的新药 C188-9,以及几种传统药物。化疗药物。十五名患者捐献者中有十名的 PSPC 对 C188-9 敏感,而一些传统化疗药物却失败了。这一发现表明,C188-9 只能对这 10 名 PSPC 患者捐赠者产生治疗效果,表明未来 PSPC 的个性化利用。© 2024。作者。
STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs.C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway.In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.© 2024. The Author(s).