Effects of different physiological levels of estradiol on chemosensitivity of HR+ breast cancer in vitro and in vivo

• Main Authors: LIU Jiashuo, XU Zhou, KONG Lingquan, ZOU Baoshan, LI Hao
• Format: Article
• Language: zho
• Published: Editorial Office of Journal of Third Military Medical University 2020-08-01
• Series: Di-san junyi daxue xuebao
• Subjects: breast cancer; estradiol; endocrine therapy; chemosensitivity
• Online Access: http://aammt.tmmu.edu.cn/Upload/rhtml/202003246.htm

Objective To investigate the effects of different phases of menstrual cycle or different physiological levels of estradiol (E2) on the chemosensitivity of breast cancer cells and bearing nude mice to epirubicin (EPI). Methods CCK-8 assay was used to observe the proliferation of MCF-7 and MDA-MB-231 cells treated with E2 (0, 50, 500, 2 500, 5 000, 10 000 pg/mL) for 24 h. After the MCF-7 and MDA-MB-231 cells were pretreated with different doses of E2 for 12 h and then with EPI alone for 24 h, the effects of E2 on the chemosensitivity of the cells to EPI were detected by CCK-8 assay. MCF-7 tumor bearing nude mice model was established after bilateral ovariectomy (OVX). The MCF-7 tumor-bearing nude mice were randomly assigned to non-OVX+EPI group (group B), OVX+EPI group (group D), OVX+E2(0.1, 5, 10 mg/kg)+EPI groups (group E, F and G) and control group. After the mice were treated with EPI, the inhibitory rate of tumor growth was calculated to detect the effects of E2 on tumor inhibition of EPI chemotherapy. Results In vitro, E2 promoted the proliferation of MCF-7 cells in a dose-dependent manner. Compared with the 50 pg/mL E2 group, the 500 pg/mL E2 group had significantly promoted proliferation in MCF-7 cells (P < 0.05). But E2 showed no significant effects on the proliferation of MDA-MB-231 cells (P>0.05). Furthermore, E2 increased chemotherapeutic efficacy of EPI on MCF-7 cells in a dose-dependent manner. The 2 500 and 5 000 pg/mL E2 groups had significantly enhanced the chemosensitivity of EPI on MCF-7 cells when compared with the 50 pg/mL E2 group (P < 0.001). But E2 had no significant effects on the chemosensitivity of EPI in MDA-MB-231 cells (P>0.05). In vivo, the tumor weights of nude mice were significantly lower in the OVX+E2+EPI groups (groups E, F and G) than the OVX+EPI group (group D) (all P < 0.01). The inhibitory rate of tumor growth was 23.3% in the non-OVX+EPI group (group B), 10.8% in the OVX+EPI group (group D), and 38.3% (group E), 37.7% (group E) and 41.3% (group E) in the OVX+E2+EPI groups. Conclusion E2 dose-dependently promotes the chemosensitivity of MCF-7 cells to EPI, suggesting that chemotherapy should be carried out in physiological periods with higher E2 level in order to improve the chemotherapy efficacy in HR+ breast cancer.