Skip to main content
. 2024 Jun 27;16(13):2354. doi: 10.3390/cancers16132354

Figure 6.

Figure 6

cSTAR model of the MDA-MB-231 cell line. (A) BMRA-reconstructed topology of the core signaling network and the connections to the DPD modules at the late time points for the MDA-MB-231 cell line. Activation and inhibition are indicated by green arrowheads and red barheads, respectively. The darker the color, the higher the absolute value of the connection coefficient. (B) Dose responses of the DPDonc to mTORi, PKCi, and their combination. The ratio of mTORi and PKCi doses in a combination is 1:2, and their doses equal 33% and 67% of the corresponding inhibitor dose when inhibitors are applied separately. (C) Predictive simulations of the Loewe isoboles demonstrate synergy by the combination of mTORi and PKCi. Solid black line represents a borderline between normal and oncogenic states, i.e., DPDonc = 0. (D–F) Model-predicted maneuvering of the MDA-MB-231 cells in Waddington’s landscape (shown by black lines). Color represents the value of Waddington’s landscape potential. After model variables reached the equilibrium, the following inhibitor doses were added at t = 0 separately or in a combination; 7 Kd PKCi (D), 10 Kd mTORi (E), or 3.5 Kd PKCi + 5 Kd mTORi (F). (D,E) Cells treated with moderate mTORi doses or large PKCi doses applied separately remain in the malignant DPDonc score area. (F) By combining these inhibitors in twice lower doses, the DPDonc trajectory shows a switch from positive to negative DPDonc scores, corresponding to non-malignant breast tissue cells.