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Experimental and Mathematical Modeling of Intracellular Calcium Dynamics for Anticancer Effects Evaluation in Esophageal Cancer
Author(s) -
Chang Yan,
Funk Marah,
Lafci Mehtap,
Stephenson Elizabeth,
Kojouharov Hristo,
Chen Benito,
Pan Zui
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.600.1
Subject(s) - intracellular , afatinib , calcium in biology , pharmacology , cancer cell , chemotherapy , cancer , cancer research , medicine , chemistry , biology , microbiology and biotechnology , erlotinib , epidermal growth factor receptor
Targeting dysregulated Ca 2+ signaling in cancer cells is an emerging chemotherapy approach. This group previously reported that store‐operated Ca 2+ entry (SOCE) blocker, such as RP4010, could effectively inhibit intracellular Ca 2+ 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 Ca 2+ 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 Ca 2+ oscillation periods in KYSE‐150 cells, an esophageal cancer cell line. The intracellular Ca 2+ oscillation period in KYSE‐150 cells was measured as ~32.8 sec; both Afatinib and RP4010 could reduce intracellular Ca 2+ 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 Ca 2+ 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 Ca 2+ oscillation period, which was further confirmed by cell proliferation analysis. This study suggests that experimental and mathematical modeling of intracellular Ca 2+ 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 .