洛拉曲克在肿瘤细胞中的药代动力学研究

Pharmacokinetics of Nolaterex in tumor cells

目的探讨新型药物洛拉曲克在肿瘤细胞中的转运特点与其敏感性之间的关系。方法采用MTT法测定洛拉曲克对三株肿瘤细胞C6、SRS-82、LoVo的生长抑制作用。通过高效液相色谱法测定经洛拉曲克处理后的细胞内外药物浓度。结果C6是三株细胞中对洛拉曲克最敏感的,SRS-82和LoVo细胞对洛拉曲克的IC50值分别是C6细胞的6.8和13.8倍。洛拉曲克在这三株细胞中胞内与胞外浓度存在线性关系。C6的细胞内稳态浓度显著高于其他两株细胞。结论本研究的结果表明,洛拉曲克可快速进入细胞,不同细胞株对洛拉曲克有不同的吸收能力,这种现象可部分解释肿瘤细胞对洛拉曲克不同的敏感性。

Objective To investigate the relationship of the transportation characteristics of Nolaterex, a new anti-cancer drug, with its sensitivity in tumor cells. Methods The sensitivities of 3 tumor cell lines (C6, SRS-82 and LoVo) to nolaterex were determined by growth inhibition test. After Nolaterex exposure, the intracellular drug concentration was measured by high-performance liquid chromatography. Results C6 was the most sensitive among the 3 cell lines, and the IC50 values of SRS-82 and LoVo cells were 6.8-fold and 13.8-fold higher, respectively, than that of C6 cells. In all the 3 cell lines, linear relationship between intracellular and extracellular drug concentrations was noted. The intracellular steady-state level achieved in C6 was significantly higher than the levels in the other two cell lines. Conclusion The results indicate that nolaterex quickly enters the cells, and different cell lines may have different nolaterex-transporting capacities, thus partially accounting for different states of sensitivity of the tumor cells to nolaterex.