Growth and Chemosensitivity of Gastric Adenocarcinoma and Non-Malignant Cell Lines in Response to Novel Anti-Cancer Drug Combinations.

Background: To design novel polychemotherapy regimens for gastric adenocarcinoma therapy with wider therapeutic windows using a novel duplex drug (D-D). Methods: Two gastric adenocarcinoma (MKN-45 and 23132/87) and 2 non-malignant (NHDF and CCL-241) cell lines were treated with different drug regimens that included different doses of the standard triple-drug combination epirubicin (E) + cisplatin (C) + 5-fluorouracil (5-FU, F), i.e. ECF, and a new D-D that combined 2′-deoxy-5-fluorouridine (5FdU) and 3′ethinylcytidine. The cells were cultured for 14 days and the effect of the drug combinations was evaluated using CASY cell counting technology. Results: Overall growth inhibition of the cell lines with ECF was not cancer cell line-specific. Replacing 5-FU in ECF with a D-D resulted in greater growth inhibition of cancer cells than of the non-malignant cell lines and the inversion of the chemosensitivity of MKN-45 and 23132/87 cells. The type and quantity of the combined drug regimen determined the cytotoxicity and chemosensitivity of the cell lines. Conclusion: The cytotoxicity and tumour-cell specificity of standard single drugs can be markedly changed and determined using multidrug combinations that include D-Ds.