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阿司匹林与2'-羟基-2,3,5'-三甲氧基查耳酮连接的聚合物胶束通过凋亡对宫颈癌的潜在抗癌作用。

Potential anticancer effect of aspirin and 2'-hydroxy-2,3,5'-trimethoxychalcone-linked polymeric micelles against cervical cancer through apoptosis.

作者信息

Lee Kang Pa, Baek Suji, Yoon Myeong Sik, Park Ji Soo, Hong Bok Sil, Lee Sang Ju, Oh Seung Jun, Kwon Seung Hae, Lee Ruda, Lee Dae Ho, Park Kang-Seo, Moon Byung Seok

机构信息

Research and Development Center, UMUST R&D Corporation, Seoul 01411, Republic of Korea.

Department of Nuclear Medicine, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.

出版信息

Oncol Lett. 2022 Jan;23(1):31. doi: 10.3892/ol.2021.13149. Epub 2021 Nov 25.

Abstract

Although early diagnosis and treatment of cancers in women are achievable through continuous diagnostic tests, cervical cancer (CVC) still has a high mortality rate. In the present study, we investigated whether certain nanoparticles (NPs), comprising aspirin conjugated 2'-hydroxy-2,3,5'-trimethoxychalcone chemicals, could induce the apoptosis of cancer cells. HeLa cells were treated with NPs and the cell viability was evaluated using WST-1 assay. Protein expression of Ki-67 was measured using immunocytochemistry. In addition, the apoptotic effect of NPs was determined using TUNEL assay. To investigate the apoptosis signaling pathways, reverse transcription quantitative PCR was performed and lipid accumulation was observed via holotomographic microscopy. The IC value of the NPs was 4.172 µM in HeLa cells. Furthermore, 10 µM NPs significantly inhibited the cell proliferation and stimulated the apoptosis of HeLa cells. In addition, apoptosis and mitochondrial dysfunction were induced by the NPs through lipid accumulation in HeLa cells, leading to apoptotic signaling cascades. Taken together, the results from the present study demonstrated that the NPs developed promoted apoptosis though efficient lipid accumulation in HeLa cells, suggesting that they may provide a novel way to improve the efficacy of CVC anticancer treatment.

摘要

尽管通过持续的诊断测试可以实现女性癌症的早期诊断和治疗,但宫颈癌(CVC)的死亡率仍然很高。在本研究中,我们研究了某些由阿司匹林共轭的2'-羟基-2,3,5'-三甲氧基查尔酮化学物质组成的纳米颗粒(NPs)是否能诱导癌细胞凋亡。用NPs处理HeLa细胞,并使用WST-1测定法评估细胞活力。使用免疫细胞化学法测量Ki-67的蛋白表达。此外,使用TUNEL测定法确定NPs的凋亡作用。为了研究凋亡信号通路,进行了逆转录定量PCR,并通过全息断层显微镜观察脂质积累。NPs在HeLa细胞中的IC值为4.172 µM。此外,10 µM NPs显著抑制HeLa细胞的增殖并刺激其凋亡。此外,NPs通过HeLa细胞中的脂质积累诱导凋亡和线粒体功能障碍,导致凋亡信号级联反应。综上所述,本研究结果表明,所开发的NPs通过在HeLa细胞中有效积累脂质促进凋亡,表明它们可能为提高CVC抗癌治疗的疗效提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/515b/8669688/be5f7f2afb12/ol-23-01-13149-g00.jpg

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