Experimental and Mathematical Modeling of Intracellular Calcium Dynamics for Anticancer Effects Evaluation in Esophageal Cancer

Abstract

Targeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. This group previously reported that store‐operated Ca2+ entry (SOCE) blocker, such as RP4010, could effectively inhibit intracellular Ca2+ oscillations and cell proliferation in esophageal cancer, a leading cancer worldwide with low 5‐year survival rate. While many current clinical chemotherapy drugs, such as tyrosine kinase inhibitors (TKIs) can induce intracellular Ca2+ release, it is not known whether combination of SOCE blockers and TKIs could achieve better chemotherapy effects. The present study employed both experimental and mathematical models to evaluate the effect of RP4010 and TKI (Afatinib) on intracellular Ca2+ oscillation periods in KYSE‐150 cells, an esophageal cancer cell line. The intracellular Ca2+ oscillation period in KYSE‐150 cells was measured as ~32.8 sec; both Afatinib and RP4010 could reduce intracellular Ca2+ and prolong the period in a dose‐dependent manner. Using a modified canonical model with variables of SOCE channel and IP3 receptor affected by RP4010 and Afatinib receptively, the intracellular Ca2+ oscillation dynamics were simulated. The theoretical data of the combined implementations of drugs also fitted well with experimental data. Both results demonstrated a synergetic effect of RP4010 and Afatinib on inhibiting intracellular Ca2+ oscillation period, which was further confirmed by cell proliferation analysis. This study suggests that experimental and mathematical modeling of intracellular Ca2+ dynamics could be used as a rapid and cost‐effective tool for evaluation of combined chemotherapy drugs.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.