Formelli F, Supino R, Cleris L, Mariani M
Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Br J Cancer. 1988 Apr;57(4):343-7. doi: 10.1038/bjc.1988.79.
The effect of the combined administration of doxorubicin (DX) and verapamil (VRP) on the induction of DX resistance of B16 melanoma cells, was investigated both in vitro and in vivo. Cells grown in the presence of increasing concentrations of DX and of 1 microM VRP, tested at several passages, were more resistant than cells grown with DX alone. The treatment of B16 melanoma bearing mice with the maximal tolerated dose of DX (12 mg kg-1 i.v.) and of VRP (25 mg kg-1 i.p.) selected a line (B16-DX. VRP) completely resistant to DX after 17 transplants, while treatment with DX alone selected a DX resistant line after 27 transplants. Lung metastases were significantly lower in the B16-DX. VRP line compared to the original B16 melanoma. The results suggest that the association of VRP with DX increases the rate of resistance development to DX.
研究了阿霉素（DX）和维拉帕米（VRP）联合给药对B16黑色素瘤细胞诱导DX耐药性的影响，包括体外和体内研究。在存在递增浓度的DX和1微摩尔VRP的情况下生长的细胞，在多个传代时进行测试，比仅用DX培养的细胞更具耐药性。用DX的最大耐受剂量（12毫克/千克静脉注射）和VRP（25毫克/千克腹腔注射）处理携带B16黑色素瘤的小鼠，经过17次传代后选择出一条对DX完全耐药的细胞系（B16-DX.VRP），而仅用DX处理则在27次传代后选择出一条DX耐药细胞系。与原始的B16黑色素瘤相比，B16-DX.VRP细胞系的肺转移明显减少。结果表明，VRP与DX联合使用会增加对DX耐药性的发展速率。
