Kurbacher C M, Wagner U, Kolster B, Andreotti P E, Krebs D, Bruckner H W
Department of Gynecology and Obstetrics, University of Bonn Medical Center, Germany.
Cancer Lett. 1996 Jun 5;103(2):183-9. doi: 10.1016/0304-3835(96)04212-7.
Utilizing a microplate ATP bioluminescence assay, two human breast carcinoma cell lines, MCF-7 and MDA-MB-231, were tested against doxorubicin (DOX), cisplatin (DDP), and paclitaxel (Tx) alone and in combination with ascorbic acid (Vit C). In both cell lines, Vit C exhibited cytotoxic activity at high concentrations (i.e. 10(2)-10(3) microM). Both cell lines also were resistant to DOX. MCF-7 was found to be DDP-resistant, MDA-MB-231 was moderately sensitive to DDP. Both cell lines were strongly sensitive to Tx. Vit C both at non-cytotoxic (1 microM) and moderately cytotoxic concentrations (10(2) microM) improved the cytotoxicity of DOX, DDP, and Tx significantly. Combination effects between Vit C and DDP or Tx were partly synergistic and partly additive or subadditive whereas a consistent synergism was found between Vit C and DOX. The mechanisms by which Vit C potentiates the cytostatics studied are yet unclear and should be evaluated further.
利用微孔板ATP生物发光测定法,对两种人乳腺癌细胞系MCF-7和MDA-MB-231进行了测试,检测它们对阿霉素(DOX)、顺铂(DDP)和紫杉醇(Tx)单独使用以及与抗坏血酸(维生素C)联合使用时的反应。在这两种细胞系中,高浓度(即10² - 10³微摩尔)的维生素C表现出细胞毒性活性。两种细胞系对阿霉素也都具有抗性。发现MCF-7对顺铂耐药,MDA-MB-231对顺铂中度敏感。两种细胞系对紫杉醇都高度敏感。在非细胞毒性浓度(1微摩尔)和中度细胞毒性浓度(10²微摩尔)下,维生素C都显著提高了阿霉素、顺铂和紫杉醇的细胞毒性。维生素C与顺铂或紫杉醇之间的联合作用部分为协同作用,部分为相加或亚相加作用,而维生素C与阿霉素之间则发现存在一致的协同作用。维生素C增强所研究的细胞抑制剂作用的机制尚不清楚,应进一步评估。