Coradini D, Biffi A, Pirronello E, Di Fronzo G
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Anticancer Res. 1995 Nov-Dec;15(6B):2557-61.
We investigated the effect of a concomitant treatment of ICI 164384 and B-interferon (beta-IFN) on the growth of estrogen-receptor-positive (ER+) and estrogen-receptor-negative (ER-) breast cancer cell lines and on their steroid receptor profiles. ICI 164384 reduced cell proliferation not only in ER+ but also in ER- cell lines and completely suppressed the stimulation induced by estradiol (E2) in hormone-sensitive cell lines, MCF7 and T47D. When associated with beta-IFN, ICI 164384 increased the inhibitory effect exerted by the low concentration of beta-IFN. Moreover, ICI 164384, singly or in association with beta-IFN, did not affect ER and PgR concentration in ER- cell lines, whereas in ER+ cell lines we observed an almost total disappearance of ER and PgR. In conclusion, our study seems to indicate that, although beta-IFN is able to control the proliferation of hormone-sensitive and hormone-independent subclones, it does not further improve the antiproliferative activity of ICI 164384. In contrast, the presence of ICI 164384, which does not induce the selection of resistant subclones under the same experimental conditions in which TAM does, may improve the efficacy of low concentration of beta-IFN and prevent the development of a secondary TAM-induced resistance.
我们研究了ICI 164384与β-干扰素(β-IFN)联合治疗对雌激素受体阳性(ER+)和雌激素受体阴性(ER-)乳腺癌细胞系生长及其类固醇受体谱的影响。ICI 164384不仅降低了ER+细胞系的细胞增殖,也降低了ER-细胞系的细胞增殖,并完全抑制了激素敏感细胞系MCF7和T47D中雌二醇(E2)诱导的刺激作用。当与β-IFN联合使用时,ICI 164384增强了低浓度β-IFN所发挥的抑制作用。此外,ICI 164384单独使用或与β-IFN联合使用时,对ER-细胞系中的ER和PgR浓度没有影响,而在ER+细胞系中,我们观察到ER和PgR几乎完全消失。总之,我们的研究似乎表明,尽管β-IFN能够控制激素敏感和激素非依赖性亚克隆的增殖,但它并不能进一步提高ICI 164384的抗增殖活性。相反,在与他莫昔芬(TAM)相同的实验条件下,ICI 164384不会诱导耐药亚克隆的产生,它可能会提高低浓度β-IFN的疗效,并防止继发性TAM诱导耐药的发生。