PO.CH01.07 · 化学
三羰基高铼酸(bathophen)铼(I)有机金属化合物在胰腺导管腺癌中的抗癌疗效
Anticancer efficacy of tricarbonylperrhenato(bathophen)rhenium(I) organometallic compound in pancreatic ductal adenocarcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
有机金属铼化合物已成为强效抗癌药物,显示出作为传统铂类药物替代品的可能性。虽然FOLFIRINOX和顺铂等铂类化疗药物常用于治疗胰腺导管腺癌(PDAC),但它们有许多副作用,如耳毒性、神经毒性、肾毒性和外周神经病变。肝毒性、心脏毒性、胃肠道毒性、血细胞减少、过敏反应、疼痛、脱发、厌食、恶病质和乏力是其他常报道的不良反应。
然而,基于铼的配体已被证明可优先对癌细胞产生细胞毒性,同时避免对健康细胞的伤害。这表明铼可能是一种更安全、更有效的癌症治疗选择。Mandal等人已生产出具有不同配体的多种铼化合物,用于一系列医药用途。在本工作中,我们评估了三羰基高铼酸(bathophen)铼(I)(PR-6)在PDAC中的治疗潜力。使用MTS法在转移性胰腺癌细胞系AsPC-1中评估了PR-6的细胞毒性作用和IC50值。PR-6在AsPC-1细胞中的IC50值被测定为5.85 μM。PR-6处理在IC50浓度下显著抑制细胞生长、迁移和存活,处理后存活率为2.3 ± 3.97%。此外,PR-6处理导致磷酸化MEK(pMEK)和磷酸化P38(pP38)蛋白表达下调,表明其对MAPK信号通路具有调节作用。根据我们的研究,PR-6在治疗胰腺癌方面具有巨大的治疗前景,并能有效改变PDAC细胞的肿瘤微环境。
查看英文原文 English abstract
Organometallic rhenium compounds have become powerful anticancer agents that show possibilities as a substitute for traditional platinum-based medications. While platinum-based chemotherapeutics like FOLFIRINOX and cisplatin are frequently used to treat pancreatic ductal adenocarcinoma (PDAC), they have a number of side effects, such as ototoxicity, neurotoxicity, nephrotoxicity, and peripheral neuropathy. Hepatotoxicity, cardiotoxicity, gastrointestinal toxicity, cytopenias, anaphylaxis, pain, alopecia, anorexia, cachexia, and asthenia are other commonly reported adverse effects.
However, ligands based on rhenium have been shown to preferentially cause cytotoxicity in cancer cells while avoiding harm to healthy cells. This suggests that rhenium could be a safer and more effective cancer treatment option. Different rhenium compounds with different ligands have been produced by Mandal et al. for a range of medicinal uses. In this work, we assessed the therapeutic potential of tricarbonylperrhenato(bathophen)rhenium(I) (PR-6) in PDAC. The cytotoxic effects and IC₅₀ value of PR-6 were assessed in the metastatic pancreatic cancer cell line AsPC-1 using the MTS assay. The IC₅₀ value for PR-6 in AsPC-1 cells was determined to be 5.85 µM. PR-6 treatment significantly inhibited cell growth, migration, and survival at the IC₅₀ concentration, with a post-treatment survival rate of 2.3 ± 3.97%. Furthermore, PR-6 treatment led to the downregulation of phosphorylated MEK (pMEK) and phosphorylated P38 (pP38) protein expression, indicating its modulatory effect on the MAPK signaling pathway. According to our research, PR-6 has a great therapeutic promise for treating pancreatic cancer and efficiently alters the tumor microenvironment in PDAC cells.
利益披露 Disclosure
I. Saha, None..
C. Parpinelli, None..
B. Varisli, None..
S. Mandal, None..
S. Bhattacharya, None.