Recombinant Human Interferon‐α2a Increases Hormone Receptor Level of a Human Breast Carcinoma Xenograft in Nude Mice and Enhances the Anti‐proliferative Activity of Tamoxifen

The effect of recombinant human interferon‐α2a (rhIFN‐α2a) 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‐α2a at a dose of 6 × 10(4) U/mouse/ day for 1 or 3 wk were not significantly different from the control, whereas those with rhIFN‐α2a at a dose of 6 × 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‐α2a was investigated using a sucrose density gradient method. The peak was only seen at 8S in both rhIFN‐α2a‐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‐α2a and TAM was compared with those of single treatments. While rhIFN‐α2a at a dose of 6 × 10(5) U/mouse/day and TAM did not show a combination effect, rhIFN‐α2a at a dose of 6 × 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‐α2a 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.