SZC010 通过调节 PI3K/Akt/NF-κB 信号通路抑制乳腺癌的发展。
SZC010 suppresses breast cancer development by regulating the PI3K/Akt/NF-κB signaling pathway.
发表日期:2024 Jun
作者:
Junhan Jiang, Xiaorui Li, Hongtao Xu, Yiwen Ma, Meiyi Fu, Xiangyu Guo, Tao Sun, Xinyu Zheng
来源:
Cellular & Molecular Immunology
摘要:
乳腺癌已成为癌症死亡的主要原因之一,也是全球女性中最常诊断出的癌症。尽管乳腺癌治疗取得了进展,但大多数患者的转移性疾病最终会由于新发或继发耐药性的发展而进展。因此,寻找高效、低毒的新药进行系统治疗极为重要。我们在本研究中应用了3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测定。分析和评估齐墩果酸 (OA) 及其衍生物对三种乳腺癌细胞系(MDA-MB-231、MCF-7 和 MDA-MB-453)的细胞毒活性。进行流式细胞术分析以了解 MDA-MB-453 细胞中 SZC010 的凋亡机制和细胞周期分析。通过蛋白质印迹评估细胞凋亡和细胞周期蛋白相关蛋白。还通过蛋白质印迹评估了 NF-κB 和 PI3K-Akt-mTOR 信号通路的关键蛋白。我们的结果表明,所有 OA 衍生物在三种类型的乳腺癌细胞系(MCF-7、MDA- MB-231 和 MDA-MB-453)。在这七种 OA 衍生物中,SZC010 在 MDA-MB-453 细胞中表现出最有效的细胞毒性。此外,我们观察到 SZC010 治疗可诱导 MDA-MB-453 细胞剂量和时间依赖性生长抑制。此外,我们证明 SZC010 通过 PI3K/Akt/mTOR 信号通路抑制 NF-κB 激活,诱导 G2/M 期生长停滞和细胞凋亡。我们的数据表明,新型 OA 衍生物 SZC010 在乳腺治疗中具有巨大潜力癌症治疗。
Breast cancer has become one of the leading causes of cancer deaths and is the most frequently diagnosed cancer among females worldwide. Despite advances in breast cancer therapy, metastatic disease in most patients will eventually progress due to the development of de novo or secondary resistance. Thus, it is extremely important to seek novel drugs with high effectiveness and low toxicity for systematic therapy.We applied a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in this study to analyze and evaluate the cytotoxic activity of oleanolic acid (OA) and its derivatives in three types of breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-453). A flow cytometry assay was performed to access the mechanisms of apoptosis and cell cycle analysis in SZC010 in MDA-MB-453 cells. Apoptosis- and cyclin-related proteins were evaluated by western blot. The key proteins of the NF-κB and PI3K-Akt-mTOR signaling pathway were also evaluated by western blot.Our results revealed that all OA derivatives were more effective than OA in three types of breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-453). Among these seven OA derivatives, SZC010 exhibited the most potent cytotoxicity in MDA-MB-453 cells. Additionally, we observed that SZC010 treatment induced dose-and time-dependent growth inhibition in MDA-MB-453 cells. Furthermore, we demonstrated that SZC010 induced growth arrest in the G2/M phase and apoptosis by inhibition of NF-κB activation via the PI3K/Akt/mTOR signaling pathway.Our data indicate that the novel OA derivative, SZC010, has great potential in breast cancer therapy.