Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province, China.
Central Laboratory, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, Jiangsu Province, China.
Arch Biochem Biophys. 2018 May 15;646:10-15. doi: 10.1016/j.abb.2018.03.029. Epub 2018 Mar 24.
Metastatic triple-negative breast cancer (TNBC) has poor outcome with conventional chemotherapy regimens due to its aggressive behavior. The acquisition of anoikis resistance, a programmed cell death process triggered by substratum detachment, is an important mechanism in TNBC metastasis. Therefore, agents that can restore the sensitivity of cancer cells to anoikis may be helpful for the treatment of metastatic TNBC. In this study, we investigated the inhibitory effect of Tubeimosides V (TBMS-V), a cyclic bisdesmoside isolated from the ethanol extracts of tubers of B. paniculatum., on anoikis resistance and the involvement of caveolin-1(CAV-1)-related signaling pathways in such process in MDA-MB-231 cells. The results showed that the treatment of TBMS-V could sensitize cancer cells to anoikis, which was associated with suppression of anchorage-independent culture-induced CAV-1 overexpression, EGFR activation as well as ITGB1-FAK activation. The data from this study might contribute to providing a potential therapeutic target for metastatic TNBC and suggest the possibility of TBMS-V and its derivatives for metastatic TNBC therapy.
转移性三阴性乳腺癌(TNBC)由于其侵袭性行为,对常规化疗方案的预后较差。获得失巢凋亡抗性,即基质脱离触发的程序性细胞死亡过程,是 TNBC 转移的重要机制。因此,能够恢复癌细胞对失巢凋亡敏感性的药物可能有助于治疗转移性 TNBC。在这项研究中,我们研究了从掌叶大黄块茎的乙醇提取物中分离得到的环双二糖 TBMS-V 对 MDA-MB-231 细胞中失巢凋亡抗性的抑制作用及其与细胞窖蛋白 1(CAV-1)相关信号通路的关系。结果表明,TBMS-V 的处理能够使癌细胞对失巢凋亡敏感,这与抑制锚定非依赖性培养诱导的 CAV-1 过表达、EGFR 激活以及 ITGB1-FAK 激活有关。这项研究的数据可能有助于为转移性 TNBC 提供潜在的治疗靶点,并表明 TBMS-V 及其衍生物有可能用于转移性 TNBC 的治疗。