Probing the Rate of Ca2+ Dependent NB Growth and Drugs Response Using Dynamic Mathematical Models

Abstract

Intracellular Ca2+ ([Ca2+]i) serves as a critical regulator of various cellular processes and plays a vital role in cellular growth, development, differentiation, and apoptosis. Several studies have reported imbalanced Ca2+ expression under pathophysiological conditions, suggesting that targeting [Ca2+]i could be a potential therapy for regulating cellular responses. In this study, we extended the work of Wacquier et al., 2016 and predicted that Ca2+ oscillatory patterns in tumorigenic cells exhibit higher Ca2+ amplitude compared to normal cells. The predicted Ca2+ oscillatory pattern is then incorporated into the cell growth model of Wallace et al., 2016 to observe its effect in both normal and SK-N-SH cells. A combined deterministic model, integrating data from both Ca2+ signaling and cell growth, is extended to a 15-day duration to observe the longterm effects of Ca2+ oscillation on growth patterns. The graphical illustrations of the simulations reveal the uncontrolled growth of SK-N-SH cells. The model is further modified to predict an optimal treatment protocol to consider the impact of different therapeutic drugs and Ca2+ modulators. The model results demonstrated that combined chemotherapy treatments lead to improved outcomes compared to using single chemotherapy. Similarly, the graphical representation of the growth patterns shows the sinusoidal behavior of the curves, indicating that the proposed chemotherapy does not completely eradicate tumorigenic cells but helps maintain the cell count at a reduced level. Our results also highlight the significant influence of Ca2+ oscillation on cell count when considering chemotherapeutic treatments