Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan
Pharmacology Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
In Vivo. 2019 Sep-Oct;33(5):1439-1445. doi: 10.21873/invivo.11622.
Endocrine therapy is clinically administered in hormone-responsive breast cancer. Combinations of fluoropyrimidine S-1 and an aromatase inhibitor or anti-estrogen are considered beneficial in Japan. Herein we assessed new combinations of S-1 and fulvestrant.
Cytotoxicity of fulvestrant and 5-fluorouracil (5-FU) was assessed in hormone-responsive (MCF-7) and non-responsive (MDA-MB-231) breast cancer cell cultures. Fulvestrant and S-1 were evaluated for antitumor activity in mice and their effects on estrogen receptor (ER)-α and progesterone receptor (PgR) levels in MCF-7 xenografts using immunohistochemical methods.
Fulvestrant inhibited growth of MCF-7, but not of MDA-MB-231 xenografts. Combinations of 5-FU and fulvestrant were superior to monotherapy in vitro. In vivo antitumor activity of S-1/fulvestrant combination therapy was significantly (p<0.05) enhanced compared to that of both monotherapies. Fulvestrant partially down-regulated expression of ERα and PgR, but in combination with S-1, it almost completely blocked their expression.
Chemo-endocrine combination therapy using S-1 and fulvestrant is beneficial in estrogen-responsive breast cancer.
内分泌疗法在激素反应性乳腺癌的临床治疗中得到应用。氟嘧啶 S-1 与芳香酶抑制剂或抗雌激素联合应用被认为在日本是有益的。在此，我们评估了 S-1 和氟维司群的新组合。
在激素反应性（MCF-7）和非反应性（MDA-MB-231）乳腺癌细胞培养物中评估氟维司群和 5-氟尿嘧啶（5-FU）的细胞毒性。用免疫组织化学方法评估氟维司群和 S-1 在 MCF-7 异种移植瘤中的抗肿瘤活性及其对雌激素受体（ER）-α和孕激素受体（PgR）水平的影响。
氟维司群抑制 MCF-7 的生长，但不抑制 MDA-MB-231 异种移植瘤的生长。5-FU 和氟维司群联合治疗在体外优于单药治疗。与单药治疗相比，S-1/氟维司群联合治疗的体内抗肿瘤活性显著增强（p<0.05）。氟维司群部分下调 ERα 和 PgR 的表达，但与 S-1 联合使用时，几乎完全阻断其表达。
使用 S-1 和氟维司群的化疗-内分泌联合治疗对雌激素反应性乳腺癌有益。
