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氯化钙和17β-雌二醇联合电化学疗法对人卵巢癌细胞活力及凋亡途径的影响

Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer.

作者信息

Łapińska Zofia, Dębiński Michał, Szewczyk Anna, Choromańska Anna, Kulbacka Julita, Saczko Jolanta

机构信息

Department of Molecular and Cellular Biology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.

出版信息

Pharmaceutics. 2020 Dec 24;13(1):19. doi: 10.3390/pharmaceutics13010019.

DOI:10.3390/pharmaceutics13010019
PMID:33374223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7823502/
Abstract

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process's effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E is not related to the change of cell membrane permeability.

摘要

雌激素（Es）在卵巢恶性肿瘤的发生和发展中起着重要作用。根据浓度不同，雌激素可能对细胞具有保护或毒性作用。此外，它们可直接或间接影响膜离子通道的活性。在本研究中，我们在体外研究了用17β-雌二醇（E；10 μM）预孵育卵巢癌细胞（MDAH - 2774）在顺铂或氯化钙常规化疗（CT）和电化学疗法（ECT）中的效果。我们使用了三种不同的电穿孔方案，包括微秒（µsEP）和纳秒（nsEP）范围。通过MTT法检测所应用治疗的细胞毒性作用。我们使用荧光染色和全息断层成像来观察形态变化。免疫细胞化学染色评估半胱天冬酶 - 12的表达。使用Yo - Pro™-1染料吸收测定法通过流式细胞仪分析电穿孔过程的有效性。我们发现用17β-雌二醇预孵育卵巢癌细胞可有效增强顺铂和氯化钙的化疗及电化学疗法。同时，雌二醇降低了电穿孔的有效性，这可能表明雌激素增加电化学疗法有效性的机制与细胞膜通透性的变化无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/587c4e01ab85/pharmaceutics-13-00019-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/38ef4471b8c8/pharmaceutics-13-00019-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/8cbc214b0761/pharmaceutics-13-00019-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/587c4e01ab85/pharmaceutics-13-00019-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/d63f04d0f62a/pharmaceutics-13-00019-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/5c21387a5fc6/pharmaceutics-13-00019-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/ddd6dd39c161/pharmaceutics-13-00019-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/341dc7a5f4f4/pharmaceutics-13-00019-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/e3c1564b120c/pharmaceutics-13-00019-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/38ef4471b8c8/pharmaceutics-13-00019-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/8cbc214b0761/pharmaceutics-13-00019-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eb7/7823502/587c4e01ab85/pharmaceutics-13-00019-g008.jpg

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