Weinreich Jürgen, Archid Rami, Bajaeifer Khaled, Hack Anita, Königsrainer Alfred, Schott Timm C
Departments of General, Visceral and Transplant Surgery, Centre of Dentistry, Oral Medicine and Maxillofacial Surgery, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
Chemotherapy. 2014;60(5-6):346-52. doi: 10.1159/000438943. Epub 2015 Aug 29.
To design novel polychemotherapy regimens for gastric adenocarcinoma therapy with wider therapeutic windows using a novel duplex drug (D-D).
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.
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.
The cytotoxicity and tumour-cell specificity of standard single drugs can be markedly changed and determined using multidrug combinations that include D-Ds.
使用新型双链体药物(D-D)设计具有更宽治疗窗的新型多化疗方案用于胃腺癌治疗。
用不同的药物方案处理两种胃腺癌细胞系(MKN-45和23132/87)以及两种非恶性细胞系(NHDF和CCL-241),这些方案包括不同剂量的标准三联药物组合表柔比星(E)+顺铂(C)+5-氟尿嘧啶(5-FU,F),即ECF,以及一种将2'-脱氧-5-氟尿苷(5FdU)和3'-乙炔基胞苷组合的新型D-D。将细胞培养14天,并使用CASY细胞计数技术评估药物组合的效果。
ECF对细胞系的总体生长抑制并非癌细胞系特异性的。用D-D替代ECF中的5-FU导致对癌细胞的生长抑制大于对非恶性细胞系的抑制,并且使MKN-45和23132/87细胞的化学敏感性发生反转。联合药物方案的类型和数量决定了细胞系的细胞毒性和化学敏感性。
使用包括D-D的多药组合可以显著改变并确定标准单一药物的细胞毒性和肿瘤细胞特异性。