Qin Lianjin, Fei Ruofan, Wang Wenjuan, He Qingjian
Department of Thyroid and Breast Surgery, First Affiliated Hospital of Huzhou University, Huzhou, China.
Cardiovascular Diagnosis and Treatment Center, First Affiliated Hospital of Huzhou University, Huzhou, China.
Transl Cancer Res. 2025 Aug 31;14(8):5109-5126. doi: 10.21037/tcr-2025-1175. Epub 2025 Aug 28.
Chemotherapy is an important therapeutic method for treating triple-negative breast cancer (TNBC), and docetaxel is the most commonly used chemotherapy drug for TNBC. Fat cells may increase the aggressiveness of TNBC and reduce the therapeutic effect of docetaxel. This research aimed to examine the mechanisms underlying the reduced chemosensitivity of TNBC to docetaxel.
Cell migration and invasion experiments revealed that breast cancer cells cocultured with mature adipocytes had increased invasive and migratory capabilities, and decreased sensitivity to docetaxel chemotherapy. Immunofluorescence and Western blot analyses revealed the significant upregulation of major vault protein (MVP) expression in the cocultured breast cancer cells.
Our findings indicated that docetaxel effectively inhibited the proliferation, migration, and invasion of the MDA-MB231 cells. The optimal therapeutic concentration for the MDA-MB231 cells was 1,000 nM, and the optimal treatment duration was 48 hours.
The level of MVP expression appears to influence the chemosensitivity of breast cancer cells to docetaxel. Notably, our results suggest that cocultured breast cancer cells may modulate MVP expression via the Notch1 signaling pathway. Overall, this study provides evidence that adipocytes could influence the chemosensitivity of TNBC cells to docetaxel via MVP expression.
化疗是治疗三阴性乳腺癌(TNBC)的重要治疗方法,多西他赛是TNBC最常用的化疗药物。脂肪细胞可能会增加TNBC的侵袭性并降低多西他赛的治疗效果。本研究旨在探讨TNBC对多西他赛化疗敏感性降低的潜在机制。
细胞迁移和侵袭实验表明,与成熟脂肪细胞共培养的乳腺癌细胞具有增强的侵袭和迁移能力,并且对多西他赛化疗的敏感性降低。免疫荧光和蛋白质印迹分析显示,共培养的乳腺癌细胞中主要穹窿蛋白(MVP)表达显著上调。
我们的研究结果表明,多西他赛有效地抑制了MDA-MB231细胞的增殖、迁移和侵袭。MDA-MB231细胞的最佳治疗浓度为1000 nM,最佳治疗持续时间为48小时。
MVP表达水平似乎影响乳腺癌细胞对多西他赛的化疗敏感性。值得注意的是,我们的结果表明,共培养的乳腺癌细胞可能通过Notch1信号通路调节MVP表达。总体而言,本研究提供了证据表明脂肪细胞可通过MVP表达影响TNBC细胞对多西他赛的化疗敏感性。