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
