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姜黄素通过NRF2/ETBR/ET-1轴预防上皮-间质转化介导的卵巢癌进展，并在顺铂给药后维持肾脏中的线粒体生物合成。

Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated Ovarian Cancer Progression through NRF2/ETBR/ET-1 Axis and Preserves Mitochondria Biogenesis in Kidney after Cisplatin Administration.

作者信息

Barinda Agian Jeffilano, Arozal Wawaimuli, Sandhiutami Ni Made Dwi, Louisa Melva, Arfian Nur, Sandora Normalina, Yusuf Muhammad

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Metabolic, Cardiovascular and Aging Cluster, Indonesian Medical Education and Research Institute (IMERI), Universitas Indonesia, Jakarta, Indonesia.

出版信息

Adv Pharm Bull. 2022 Jan;12(1):128-141. doi: 10.34172/apb.2022.014. Epub 2020 Sep 19.

DOI:10.34172/apb.2022.014
PMID:35517894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9012927/
Abstract

Ovarian carcinoma is one of the gynaecological malignancies that have the highest mortality rates due to its progressivity. Endothelin signalling plays a leading role in the progression of ovarian cancer through Epithelial-to-Mesenchymal Transition (EMT). Cisplatin commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic effect. Curcumin, a turmeric-derived compound, has an anticancer property, as well as a renal protective effect. Moreover, curcumin augments the affinity of the antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of curcumin on ovarian cancer progression and cisplatin-induced kidney injury remain unknown. Curcumin was used as a supplementary therapy together with cisplatin in Human Ovarian Cancer Cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after cisplatin ± curcumin administration will also be analyzed Co-treatment of cisplatin with curcumin enhanced the expression of a gene involved in apoptosis in association with NRF2 enhancement, thus activated ETBR-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, curcumin treatment improved mitochondria biogenesis markers such as PGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis in kidney isolated from cisplatin-treated ovarian cancer rat. Curcumin could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of cisplatin treatment in the clinical setting.

摘要

卵巢癌是死亡率最高的妇科恶性肿瘤之一，因其具有侵袭性。内皮素信号传导通过上皮-间质转化（EMT）在卵巢癌进展中起主导作用。顺铂是常用的强效化疗药物，但其应用因肾毒性作用而受到阻碍。姜黄素是一种从姜黄中提取的化合物，具有抗癌特性以及肾脏保护作用。此外，姜黄素可增强抗氧化酶的亲和力，同时抑制内皮素-1（ET-1）信号传导。姜黄素对卵巢癌进展和顺铂诱导的肾损伤的影响尚不清楚。在人卵巢癌细胞系（SKOV3）以及啮齿动物诱导的卵巢癌模型中，姜黄素与顺铂联合用作辅助治疗。还将分析顺铂±姜黄素给药后卵巢癌大鼠模型的肾脏表型。顺铂与姜黄素联合治疗增强了与NRF2增强相关的凋亡相关基因的表达，从而激活了SKOV3细胞和大鼠卵巢癌模型中ETBR介导的ET-1清除。此外，姜黄素治疗改善了线粒体生物发生标志物，如PGC-1α和TFAM，并预防了顺铂治疗的卵巢癌大鼠肾脏中ET-1介导的肾纤维化和细胞凋亡的增加。姜黄素可能作为一种具有肾脏保护作用的抗癌佐剂添加，从而在临床环境中提高顺铂治疗的疗效和安全性。

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