Work

Investigating the mechanism of inositol against paclitaxel chemoresistance on triple-negative breast cancer by using 7T multiparametric MRI and mitochondrial changes

Year: 2025

Type: article

Abstract: BACKGROUND: The emerging triple-negative breast cancer (TNBC) treatments target mitochondrial fission to combat paclitaxel (PTX) resistance. Inositol's inhibition of this process makes it a potential therapy. Multiparametric MRI provides an early and effective assessment of these innovations. OBJECTIVE: To monitor the efficacy of Inositol on PTX-resistant TNBC mice using 7T multiparametric MRI, and to further explore the mechanism of inositol inhibiting PTX chemoresistance in combination with the morphological changes of isolated mitochondria. MATERIALS AND METHODS: BALB/c mice aged 6-8 weeks were subcutaneously inoculated with PTX-resistant 4T1 cells and divided into three groups: PTX-treated mice (n = 24), "PTX + Inositol"-treated mice (n = 24) and untreated mice (n = 24). Six mice in each group underwent diffused weighted imaging (DWI) and diffusion kurtosis imaging (DKI) every 7 days after administration. To observe the dynamic changes of inositol within the tumor tissue post-treatment, chemical exchange saturation transfer (CEST) imaging was performed. Six mice in each group were sacrificed on day 0, 7, and 14 respectively for histopathological examination. After a 3-week scanning cycle, the remaining mice in each group were euthanized for histopathological analysis. The therapeutic response of inositol was assessed via Hematoxylin & Eosin (H&E) staining and Ki-67 immunohistochemistry. The effects of inositol on mitochondrial structure and PTX resistance were studied by Western Blot and electron microscopy. One-way analysis of variance, independent samples t-test, paired samples t-test, Kruskal-Wallis, and Spearman rank correlation were used. RESULTS: , p < 0.001). The MD, MK, and ADC values were correlated significantly with tumor cell density (MD, r = -0.872; MK, r = 0.723; ADC, r = -0.858) and Ki-67 level (MD, r = -0.975; MK, r = 0.680; ADC, r = -0.860). The p-AMPK levels of PTX + Ins group were lower than that of PTX group (0.50 ± 0.06 vs. 0.60 ± 0.05, p = 0.04), and the mitochondrial length was longer than that of PTX group (0.86 ± 0.10 vs. 0.44 ± 0.09, p < 0.001), with a significant correlation to Ki-67 levels (r = -0.853, p < 0.001). CONCLUSION: Inositol may counteract PTX resistance in TNBC by disrupting mitochondrial fission, and DWI combined with DKI effectively tracked this effect.

Source: Breast Cancer Research

DOI: 10.1186/s13058-025-02051-4