Effects of different physiological levels of estradiol on chemosensitivity of HR+ breast cancer <italic style="font-style: italic">in vitro</italic> and <italic style="font-style: italic">in vivo</italic>

Jiashuo LIU; Zhou XU; Lingquan KONG; Baoshan ZOU; Hao LI; Kainan WU

doi:10.16016/j.1000-5404.202003246

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

Basic Medicine | 更新时间：2026-01-09

- Effects of different physiological levels of estradiol on chemosensitivity of HR+ breast cancer in vitro and in vivo
- Journal of Third Military Medical University Vol. 42, Issue 15, Pages: 1531-1535, 1554(2020)
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院内分泌乳腺外科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202003246
  CLC： R347.913;R73-361;R737.9
- Received：16 March 2020，
  
  Revised：2020-05-09，
  
  Published：15 August 2020
- 稿件说明：
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Jiashuo LIU, Zhou XU, Lingquan KONG, et al. Effects of different physiological levels of estradiol on chemosensitivity of HR+ breast cancer in vitro and in vivo[J]. Journal of Third Military Medical University, 2020, 42(15): 1531-1535, 1554.
DOI：

Jiashuo LIU, Zhou XU, Lingquan KONG, et al. Effects of different physiological levels of estradiol on chemosensitivity of HR+ breast cancer in vitro and in vivo[J]. Journal of Third Military Medical University, 2020, 42(15): 1531-1535, 1554. DOI： 10.16016/j.1000-5404.202003246.

摘要

目的

探讨月经周期不同时相及妊娠期雌激素(estradiol

E2)水平对乳腺癌细胞及荷瘤裸鼠表柔比星(epirubicin，EPI)化疗敏感性的影响。

方法

CCK-8检测不同浓度E2(0、50、500、2 500、5 000、10 000 pg/mL)处理24 h分别对MCF-7、MDA-MB-231细胞增殖活性的影响；不同浓度E2预处理12 h后，EPI单独处理24 h，观察E2对EPI化疗敏感性及疗效的影响。建立双侧卵巢切除(OVX)MCF-7荷瘤裸鼠模型，设立Non-OVX+EPI化疗组(B组)，OVX+EPI化疗组(D组)

OVX+E2(0.1、5、10 mg/kg)+EPI化疗组(E、F、G组)及对应对照组(A、C组)，通过测量瘤质量并计算抑瘤率，检测不同水平E2(0.1、5、10 mg/kg)及卵巢去势对EPI(5 mg/kg)抑瘤作用的影响。

结果

E2呈剂量依赖性促进MCF-7细胞的增殖，500 pg/mL E2组细胞增殖活性较50 pg/mL E2组显著增强(

0.05)。E2对MDA-MB-231细胞增殖影响不明显，组间差异无统计学意义(

0.05)。E2呈剂量依赖性增强EPI对MCF-7细胞的化疗杀伤作用，

与50 pg/mL E2组比较，2 500、5 000 pg/mL E2组均显著增强EPI的化疗敏感性(

0.01)。E2对MDA-MB-231细胞EPI化疗敏感性影响无统计学意义(

0.05)。MCF-7荷瘤裸鼠模型中，OVX+E2+EPI化疗组(E、F、G组)的平均瘤质量均显著低于OVX+EPI化疗组(D组，

0.01)。Non-OVX+EPI化疗组(B组)抑瘤率为23.3%，OVX+EPI化疗组(D组)抑瘤率为10.8%，OVX+E2+EPI化疗组的抑瘤率分别为E组38.3%、F组37.7%、G组41.3%。

结论

不同生理时期雌激素呈剂量依赖性增强MCF-7细胞对EPI的化疗敏感性，提示在雌激素水平较高的生理时期应用化疗药物，有望提高HR+乳腺癌的疗效。

Abstract

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

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

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 (

0.05). But E2 showed no significant effects on the proliferation of MDA-MB-231 cells (

0.05). Furthermore

E2 increased chemotherapeutic efficacy of E

PI 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 (

0.001). But E2 had no significant effects on the chemosensitivity of EPI in MDA-MB-231 cells (

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

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.

关键词

Keywords

references

SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2015[J]. CA: A Cancer J Clin, 2015, 65(1): 5-29. DOI:10.3322/caac.21254.

AHMED S S, THIKE A A, ZHANG K, et al . Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group[J ] . J Clin Pathol, 2017, 70(4): 320-326. DOI:10.1136/jclinpath-2016-203847.

LUO Q Q, HUANG J B, WU Y T, et al . Tidal chemotherapy in premenopausal patients with hormone receptor positive breast cancer[J ] . Med Hypotheses, 2017, 102: 4-7. DOI:10.1016/j.mehy.2017.03.003.

HUANG J B, JI G Y, XING L, et al . Neo-endocrinochemotherapy: a novel approach for enhancing chemotherapeutic efficacy in clinic?[J ] . Med Hypotheses, 2013, 80(4): 441-446. DOI:10.1016/j.mehy.2012.12.037.

BEDOSCHI G, NAVARRO P A, OKTAY K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact[J]. Future Oncol, 2016, 12(20): 2333-2344. DOI:10.2217/fon-2016-0176.

HUANG J B, JIN L B, JI G Y, et al . Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine[J ] . BMC Cancer, 2013, 13: 334. DOI:10.1186/1471-2407-13-334.

HUANG J B, JI G Y, XING L, et al . Chemosensitization role of endocrine hormones in cancer chemotherapy[J ] . Chin Med J, 2013, 126(1): 175-180.

BEZWODA W R, MEYER K. Effect of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF 7 cells[J]. Cancer Res, 1990, 50(17): 5387-5391.

TIAN J M, RAN B, ZHANG C L, et al . Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression[J ] . Revista Brasileira De Pesquisas Med E Biol, 2018, 51(3): 1-7. DOI:10.1590/1414-431X20175612.

HUG V, HORTOBAGYI G N, DREWINKO B, et al . Tamoxifen-citrate counteracts the antitumor effects of cytotoxic drugs in vitro [J ] . J Clin Oncol, 1985, 3(12): 1672-1677. DOI:10.1200/JCO.1985.3.12.1672..

WOODS K E, RANDOLPH J K, GEWIRTZ D A. Antagonism between tamoxifen and doxorubicin in the MCF-7 human breast tumor cell line[J]. Biochem Pharmacol, 1994, 47(8): 1449-1452. DOI:10.1016/0006-2952(94)90346-8.

WEICHSELBAUM R R, HELLMAN S, PIRO A J, et al . Proliferation kinetics of a human breast cancer line in vitro following treatment with 17beta-estradiol and 1-beta-D-arabinofuranosylcytosine[J ] . Cancer Res, 1978, 38(8): 2339-2342..

HUG V, JOHNSTON D, FINDERS M, et al . Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors[J ] . Cancer Res, 1986, 46(1): 147-152..

OSBORNE C K, HOBBS K, CLARK G M. Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice[J]. Cancer Res, 1985, 45(2): 584-590.

邢雷, 黄剑波, 孔令泉, 等.妊娠乳腺癌患者2例终止妊娠前或后行首疗程化疗的疗效分析并文献复习[J].重庆医科大学学报, 2013, 38(2): 220-221. DOI:10.3969/j.issn.0253-3626.2013.02.029.

XING L, HUANG J B, KONG L Q, et al . Effect of chemotherapy before or after termination in pregnancy-associated breast cancer patients: two cases report[J ] . J Chongqing Med Univ, 2013, 38(2): 220-221. DOI:10.3969/j.issn.0253-3626.2013.02.029.

STOVER D G, COLOFF J L, BARRY W T, et al . The role of proliferation in determining response to neoadjuvant chem otherapy in breast cancer: a gene expression-based meta-analysis[J ] . Clin Cancer Res, 2016, 22(24): 6039-6050. DOI:10.1158/1078-0432.CCR-16-0471.

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

DOI：10.16016/j.1000-5404.202003246

摘要

Abstract

关键词

Keywords

references