Gene expression of Fulvestrant induced control (FC), dormancy-like (FD) or relapse (FR) cell samples

To generate a dormancy state in vivo, ovariectomized female BALB/c athymic mice (simulating the post-menopausal state) with ER+MC cell (MCF7) derived xenografts were treated with Fulvestrant (FUL). Throughout the treatment period, no significant differences in the body weight of the FUL-treated groups (FD and FR) compared to the vehicle-treated groups (FC) were observed. Whereas xenografts in the vehicle-treated group (as control group: FC) continued to increase in volume, the xenograft volumes of the FUL-treated group regressed 20%-30% in the first week and then remained stable during the four-week administration of FUL. Thereafter, half of the xenografts in FUL-treated mice were resected at random and designated as a dormancy-like group (FD). For the remaining FUL treated xenografts, treatment was discontinued and xenograft volume was observed to gradually increase. This group was defined as the relapse group (FR) and would mimic relapses observed after discontinuation of anti-estrogen therapy in patients. The FC, FD or FR cell lines were established in vitro from their corresponding xenografts for RNA-sequencing.

为构建体内休眠状态模型，本研究对携带雌激素受体阳性MCF7细胞（ER+MCF7）来源异种移植瘤的去卵巢雌性BALB/c裸小鼠（模拟绝经后状态）施以氟维司群（FUL）治疗。整个给药周期内，氟维司群给药组（FD、FR组）与赋形剂对照组（FC组）的小鼠体重均无显著差异。赋形剂处理组（即对照组FC）的异种移植瘤体积持续增长，而氟维司群给药组的异种移植瘤体积在给药第一周即退缩20%~30%，并在后续四周的给药过程中维持稳定。此后，本研究随机切除氟维司群给药小鼠体内一半的异种移植瘤，将其命名为休眠样组（FD）。对于剩余的氟维司群给药异种移植瘤，研究人员停止给药，观测到其瘤体逐渐增大，该组被定义为复发组（FR），可模拟患者接受抗雌激素治疗停药后出现的肿瘤复发情况。本研究分别从FC、FD、FR组对应的异种移植瘤中体外培养建立对应细胞系，用于RNA测序（RNA-sequencing）。