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

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-07 DOI:10.1007/s00280-024-04671-7
Rui Xu, Xiaowen Yang, Bin Tang, Yifan Mao, Feiyun Jiang
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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.

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全反式维甲酸与他莫昔芬联合治疗可抑制卵巢癌。
背景:卵巢癌是女性生殖系统的恶性肿瘤,死亡率高达 70%:卵巢癌是女性生殖系统的恶性肿瘤,死亡率高达 70%。雌激素受体α(ERα)阳性的卵巢癌患者占所有卵巢癌患者的大多数。ERα可促进肿瘤的生长和增殖:方法:全反式维甲酸(ATRA)和他莫昔芬的联合作用是通过 MTS 对他莫昔芬和化合物库进行联合筛选得到的。此外,我们还采用了集落形成试验、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等方法,进一步评估了他莫昔芬和ATRA在体外和体内对ER-α阳性卵巢癌的疗效:结果:我们的研究发现,全反式维甲酸(ATRA)可与他莫昔芬协同作用,导致细胞周期停滞和凋亡,抑制体内和体外ERα阳性卵巢癌。对其机制的进一步探讨发现,ATRA 可抑制 ERα 信号通路相关基因,提高 ERα 阳性卵巢癌细胞对他莫昔芬的敏感性,并确定他莫昔芬和 ATRA 作为 ERα 阳性卵巢癌治疗药物的有效性:结论:ATRA 和他莫昔芬联合应用是治疗 ERα 阳性卵巢癌的新方法。
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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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