Angioli R, Untch M, Sevin B U, Steren A, Hightower R D, Perras J P, Nguyen H N, Koechli O R, Averette H E
Department of Obstetrics and Gynecology, University of Miami School of Medicine, Florida.
Cancer. 1993 May 1;71(9):2776-81. doi: 10.1002/1097-0142(19930501)71:9<2776::aid-cncr2820710915>3.0.co;2-r.
Interferon (IFN) has been reported to increase hormone receptor expression in breast cancer cells and to sensitize them to antiproliferative hormones. Endometrial cancer cells with high progesterone receptor (PR) level respond better to progesterone therapy than cells with either low or absent PR level. The effect of four different interferons (alpha and beta, both natural [n] and recombinant [r]) on cell proliferation and steroid receptor levels was investigated in the PR positive AE-7 human endometrial cancer cell line over a period of 12 days.
Cells were exposed to 10,100 and 1000 IU/ml of each IFN either for 3 days or continuously for 12 days. Hormone receptors were determined by the monoclonal enzyme immunoassay. Chemosensitivity was evaluated with the adenosine triphosphate-cell viability assay.
AE-7 has a low level of estrogen receptors, which was not significantly affected by IFN exposure. The four IFN showed significantly enhanced PR levels over 12 days in both the 3-day and continuous-exposure experiments. No significant difference of PR enhancement was observed between 3 days and continuous exposure to IFN. This increase of receptors did not appear to be dose related. IFN enhanced PR level to a maximum level of about two times control cells. IFN did not produce significant cytotoxicity. Antiproliferative activity was observed with nIFN beta and rIFN beta at 1000 IU/ml dose in continuous-exposure experiments, which showed survival values of 79% and 69% respectively, compared with control at day 12.
These preliminary data on PR expression modulation support other studies, which have shown that IFN modulate hormone receptor expression and, therefore, may play a role in the treatment of endometrial cancer.
据报道，干扰素（IFN）可增加乳腺癌细胞中激素受体的表达，并使其对抗增殖激素敏感。孕酮受体（PR）水平高的子宫内膜癌细胞比PR水平低或无PR的细胞对孕酮治疗反应更好。在PR阳性的AE-7人子宫内膜癌细胞系中，研究了四种不同的干扰素（α和β，天然[n]和重组[r]）在12天内对细胞增殖和类固醇受体水平的影响。
将细胞暴露于每种干扰素的10、100和1000 IU/ml浓度下，持续3天或连续12天。通过单克隆酶免疫测定法测定激素受体。用三磷酸腺苷-细胞活力测定法评估化学敏感性。
AE-7的雌激素受体水平较低，IFN暴露对其无显著影响。在3天和连续暴露实验中，四种干扰素在12天内均显著提高了PR水平。3天和连续暴露于干扰素之间，PR增强无显著差异。这种受体增加似乎与剂量无关。干扰素将PR水平提高到约为对照细胞两倍的最高水平。干扰素未产生显著的细胞毒性。在连续暴露实验中，天然β干扰素（nIFN beta）和重组β干扰素（rIFN beta）在1000 IU/ml剂量下观察到抗增殖活性，在第12天与对照相比，存活率分别为79%和69%。
这些关于PR表达调节的初步数据支持了其他研究，这些研究表明IFN可调节激素受体表达，因此可能在子宫内膜癌的治疗中发挥作用。
