Hoferová Z, Fedorocko P, Hofer M, Hofmanová J, Kozubík A, Eliásová V
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Neoplasma. 2003;50(2):102-9.
Nordihydroguaiaretic acid (NDGA) and esculetin, both nonspecific inhibitors of lipoxygenases (LOX), were found to suppress expressively the in vitro proliferation of fibrosarcoma cells G5:113 in concentrations ranging from 10 to 50 microM. Subsequent flow-cytometric analysis of the cell cycle showed that both these drugs significantly decreased the percentage proportion of cells in the G0/G1-phase and simultaneously increased significantly this proportion in the S-phase. No apoptosis was detected in the whole range of concentrations studied, from 2.5 to 50 mM. On the contrary, in experiments in vivo, neither NDGA nor esculetin had any curative effect if they were repeatedly injected intraperitoneally (i.p.) into mice bearing tumors growing from subcutaneously (s.c.) transplanted G5:113 cells. Pretreatment of the fibrosarcoma cells with NDGA or esculetin in vitro preceding their s.c. transplantation into mice did not result in suppression of the tumor growth, either. Finally, if G5:113 cells were injected intravenously and the mice were subsequently treated repeatedly with i.p. injections of NDGA, decreased survival and increased number of surface lung metastases were observed in the NDGA-treated group. Thus the suppressive action of inhibitors of LOX on the growth of fibrosarcoma cells in vitro was not reflected in their anti-tumor effects in vivo.
去甲二氢愈创木酸（NDGA）和七叶亭，这两种脂氧合酶（LOX）的非特异性抑制剂，被发现能在10至50微摩尔的浓度范围内显著抑制纤维肉瘤细胞G5:113的体外增殖。随后对细胞周期的流式细胞术分析表明，这两种药物均显著降低了G0/G1期细胞的百分比比例，同时显著增加了S期细胞的这一比例。在所研究的2.5至50毫摩尔的整个浓度范围内均未检测到细胞凋亡。相反，在体内实验中，如果将NDGA和七叶亭反复腹腔注射（i.p.）到皮下（s.c.）移植G5:113细胞后生长肿瘤的小鼠体内，它们均没有任何治疗效果。在将纤维肉瘤细胞皮下移植到小鼠体内之前，先用NDGA或七叶亭在体外对其进行预处理，也不会导致肿瘤生长受到抑制。最后，如果静脉注射G5:113细胞，随后对小鼠反复进行腹腔注射NDGA治疗，在接受NDGA治疗的组中观察到存活率降低和肺表面转移灶数量增加。因此，LOX抑制剂对纤维肉瘤细胞体外生长的抑制作用在其体内抗肿瘤作用中并未体现出来。
