UNASSIGNED: Cells were treated with tamoxifen or trastuzumab to examine their role in bidirectional crosstalk. The molecule mechanism of miR-770-5p on HER2/EGFR/IGF1R bidirectional crosstalk was explored by western blot. The expression of miR-770-5p in trastuzumab resistant cells was examined by q-PCR. To investigate the effect of miR-770-5p on cancer cell proliferation in trastuzumab resistance state, resistant cells were analyzed by iCELLigence real-time cell analyzer.
UNASSIGNED: miR-770-5p expression was significantly downregulated in trastuzumab-resistant BT-474 and SK-BR-3 cells. Overexpression of miR-770-5p sensitized the resistant cells to trastuzumab, as evidenced by reduced cell proliferation and increased cell viability. Additionally, in resistant cells, increased expression and activation of EGFR and IGF1R were observed. However, miR-770-5p overexpression resulted in decreased phosphorylation of AKT and ERK, indicating its suppressive role in EGFR/HER2 signaling. Furthermore, miR-770-5p downregulated the expression of IGF1R and mTOR, suggesting its involvement in regulating the escape signaling mediated by IGF1R in resistance.
UNASSIGNED: In conclusion, our findings demonstrate the critical role of miR-770-5p in regulating bidirectional crosstalk and overcoming trastuzumab resistance in breast cancer cells. These results highlight the potential of miR-770-5p as a therapeutic target to improve the efficacy of targeted therapies and address resistance mechanisms in breast cancer.
■用他莫昔芬或曲妥珠单抗处理细胞以检查它们在双向串扰中的作用。通过westernblot探讨miR-770-5p对HER2/EGFR/IGF1R双向串扰的分子机制。通过q-PCR检测miR-770-5p在曲妥珠单抗抗性细胞中的表达。探讨miR-770-5p对曲妥珠单抗耐药状态下癌细胞增殖的影响,用iCELLigence实时细胞分析仪分析耐药细胞。
■miR-770-5p表达在曲妥珠单抗抗性BT-474和SK-BR-3细胞中显著下调。miR-770-5p的过表达使耐药细胞对曲妥珠单抗敏感,如减少的细胞增殖和增加的细胞活力所证明的。此外,在抗性细胞中,观察到EGFR和IGF1R的表达和激活增加。然而,miR-770-5p过表达导致AKT和ERK磷酸化降低,表明其在EGFR/HER2信号传导中的抑制作用。此外,miR-770-5p下调IGF1R和mTOR的表达,提示其参与调节抗性中IGF1R介导的逃逸信号。
■总而言之,我们的研究结果表明,miR-770-5p在调节乳腺癌细胞双向串扰和克服曲妥珠单抗耐药方面的关键作用.这些结果突出了miR-770-5p作为治疗靶标以提高靶向疗法的功效和解决乳腺癌耐药机制的潜力。