全反式维甲酸联合他莫昔芬治疗卵巢癌。

Combined treatment of All-trans retinoic acid with Tamoxifen suppresses ovarian cancer.

机构信息

Department of Gynecology, East China Normal University Wuhu Affiliated Hospital, The Second People's Hospital of Wuhu City, No.259, Middle Jiuhua Road, Jinghu District, Wuhu, 241000, China.

Department of Electrocardiogram, East China Normal University Wuhu Affiliated Hospital, The Second People's Hospital of Wuhu City, No.259, Middle Jiuhua Road, Jinghu District, Wuhu, 241000, China.

出版信息

Cancer Chemother Pharmacol. 2024 Aug;94(2):259-270. doi: 10.1007/s00280-024-04671-7. Epub 2024 May 7.

DOI:10.1007/s00280-024-04671-7

PMID:38714534

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390921/

Abstract

BACKGROUND

Ovarian cancer is a malignant tumor of the female reproductive system, and its mortality rate is as high as 70%. Estrogen receptor α (ERα)-positive ovarian cancer accounted for most of all ovarian cancer patients. ERα can promote the growth and proliferation of tumors.

METHODS

The combined effect of All-trans retinoic acid (ATRA) and tamoxifen was obtained by the combination screening of tamoxifen and compound library by MTS. In addition, colony formation assay, flow cytometry analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blot, and tumor xenotransplantation models were used to further evaluate the efficacy of tamoxifen and ATRA in vitro and in vivo for ER-α-positive ovarian cancer.

RESULTS

In our study, we found that All-trans retinoic acid (ATRA) can cooperate with tamoxifen to cause cell cycle arrest and apoptosis and inhibit ERα-positive ovarian cancer in vivo and in vitro. Further exploration of the mechanism found that ATRA can Inhibit genes related to the ERα signaling pathway, enhance the sensitivity of ERα-positive ovarian cancer cells to tamoxifen, and ascertain the effectiveness of tamoxifen and ATRA as treatments for ovarian cancer with an ERα-positive status.

CONCLUSION

Combination of ATRA and tamoxifen is a new way for the treatment of ERα-positive ovarian cancer.

摘要

背景

卵巢癌是女性生殖系统的一种恶性肿瘤，其死亡率高达 70%。雌激素受体α（ERα）阳性卵巢癌占所有卵巢癌患者的大多数。ERα 可以促进肿瘤的生长和增殖。

方法

通过 MTS 对他莫昔芬和化合物文库进行联合筛选，获得全反式维甲酸（ATRA）和他莫昔芬的联合作用。此外，还通过集落形成实验、流式细胞术分析、免疫荧光染色、实时定量聚合酶链反应（PCR）、Western blot 和肿瘤异种移植模型，进一步评估了他莫昔芬和 ATRA 对 ER-α阳性卵巢癌的体内外疗效。

结果

在我们的研究中，我们发现全反式维甲酸（ATRA）可以与他莫昔芬协同作用，导致细胞周期停滞和凋亡，并抑制体内和体外的 ERα 阳性卵巢癌。进一步的机制探索发现，ATRA 可以抑制与 ERα 信号通路相关的基因，增强 ERα 阳性卵巢癌细胞对他莫昔芬的敏感性，证实了他莫昔芬和 ATRA 作为治疗 ERα 阳性卵巢癌的有效性。