Fig. 7: Sensitization of luminal IntClust2 cell lines expressing AAMDC by co-treatment with PI3K-AKT-mTORC1 blockers in combination with tamoxifen. | Nature Communications

Fig. 7: Sensitization of luminal IntClust2 cell lines expressing AAMDC by co-treatment with PI3K-AKT-mTORC1 blockers in combination with tamoxifen.

From: The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer

Fig. 7

a Pharmacological blockade of PI3K-AKT-mTOR leads to downregulation of MTHFD1L expression in estrogen receptor positive (ER+) intercluster 2 (IntClust2) breast cancer cell lines (SUM44PE and MDA-MB-134) treated with tamoxifen (Tam, 5 μM) in combination with dactolisib or everolimus (24 h, at the concentrations indicated in the blots). Source data are provided as a Source Data file. b–d Dose-dependent changes in cell viability in the ER+ breast cancer cell lines MDA-MB-134 (b), SUM44PE (c), and T-47D (d) treated with dactolisib (Dacto., top, blue) or everolimus (Evero., bottom, blue), with tamoxifen (Tam., red) and as combinations (green). Data are presented as mean values ± SD. n = 3 biologically independent experiments. Viability is determined using a luminescence assay (CellTiter-Glo®) after 72 h post-treatment. e Tamoxifen and selected inhibitors of the PI3K-AKT-mTOR pathway exhibit synergistic pharmacological interactions in inhibiting tumor cell viability. Plots indicating the combination index (CI) for tamoxifen with dactolisib (purple) and tamoxifen with everolimus (cyan) in MDA-MB-134 (left), SUM44PE (middle), and T-47D (right) cells. CI < 1 synergistic, CI = 1 additive, and CI > 1 antagonistic. The CI is calculated from the average of three independent cell viability assays by the CI index method. Fraction affected is the fraction of non-viable cells. f Dose-dependent changes in cell viability in the MCF-7 cell line stably overexpressing AAMDC cDNA compared to empty vector (EV) treated with dactolisib, everolimus, and docetaxel. Statistical significance is determined for biological triplicates and presented as mean values ± SD and p-values are determined by multiple unpaired t-tests. For dactolisib, from left to right: **p = 0.0007, **p = 0.0013, **p = 0.0016, ***p < 0.0001, ***p < 0.0001; for everolimus, from left to right: *p = 0.0062, *p = 0.0053, *p = 0.0066. Bottom right: Relative AAMDC mRNA expression in a panel of ER+ breast cancer cell lines normalized to the non-tumorigenic epithelial line MCF-12A, as assessed by qRT-PCR. Data presented as mean values ± SD and p-values are determined by two-tailed unpaired t-test with Welch’s correction (*p = 0.0308, **p = 0.0012, ***p = 0.0001).

Back to article page