Josui K, Kubota T, Kitajima M
Department of Surgery, School of Medicine, Keio University, Tokyo.
Jpn J Cancer Res. 1992 Dec;83(12):1347-53. doi: 10.1111/j.1349-7006.1992.tb02768.x.
The effect of recombinant human interferon-alpha 2a (rhIFN-alpha 2a) on the hormone receptor level and antitumor activity of tamoxifen (TAM) was investigated in nude mice using ZR-75-1, an estrogen receptor (ER)-positive, and progesterone receptor (PgR)-negative human breast carcinoma xenograft. ER levels (maximum binding sites) of tumors treated with rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day for 1 or 3 wk were not significantly different from the control, whereas those with rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day for 1 or 3 wk were higher than the control (3.9- to 4.4-fold) with a significant difference at P < 0.01. The increase of ER by rhIFN-alpha 2a was investigated using a sucrose density gradient method. The peak was only seen at 8S in both rhIFN-alpha 2a-treated tumor and control ER, and the sedimentation patterns were almost the same, suggesting that both ERs were essentially equivalent. On the other hand, PgR of all the treated groups could be detected, while that of the control group was undetectable. The antitumor effect of the combination treatment of rhIFN-alpha 2a and TAM was compared with those of single treatments. While rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day and TAM did not show a combination effect, rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day and TAM showed a synergistic combination effect, and ER was decreased to the threshold of detection by the combination treatment. These findings indicated that a low dose of rhIFN-alpha 2a increased the ER levels of ER-positive human breast cancer in vivo as well as in vitro and enhanced the anti-proliferative effect of TAM, and the newly synthesized ER was essentially the same as the original ER.
使用雌激素受体（ER）阳性且孕激素受体（PgR）阴性的人乳腺癌异种移植瘤ZR-75-1，在裸鼠中研究了重组人干扰素α-2a（rhIFN-α2a）对他莫昔芬（TAM）激素受体水平和抗肿瘤活性的影响。以6×10⁵ U/小鼠/天的剂量给予rhIFN-α2a 1或3周，处理后的肿瘤ER水平（最大结合位点）与对照组无显著差异；而以6×10⁴ U/小鼠/天的剂量给予rhIFN-α2a 1或3周，其ER水平高于对照组（3.9至4.4倍），P<0.01，差异有统计学意义。使用蔗糖密度梯度法研究了rhIFN-α2a对ER的增加作用。在rhIFN-α2a处理的肿瘤和对照ER中，峰值均仅出现在8S处，沉降模式几乎相同，表明两种ER基本相同。另一方面，所有处理组均可检测到PgR，而对照组未检测到。比较了rhIFN-α2a与TAM联合治疗和单一治疗的抗肿瘤效果。虽然以6×10⁵ U/小鼠/天的剂量给予rhIFN-α2a和TAM未显示联合效应，但以6×10⁴ U/小鼠/天的剂量给予rhIFN-α2a和TAM显示出协同联合效应，联合治疗使ER降至检测阈值以下。这些发现表明，低剂量的rhIFN-α2a在体内和体外均可增加ER阳性人乳腺癌的ER水平，并增强TAM的抗增殖作用，新合成的ER与原始ER基本相同。
