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Biological effects in photodynamic treatment combined with electropermeabilization in wild and drug resistant breast cancer cells
Bioelectrochemistry ( IF 4.8 ) Pub Date : 2018-04-19 , DOI: 10.1016/j.bioelechem.2018.04.008
Joanna Weżgowiec , Julita Kulbacka , Jolanta Saczko , Joanna Rossowska , Grzegorz Chodaczek , Małgorzata Kotulska

Electrochemotherapy became one of the therapeutic protocols successfully used in oncology. However, biological effects occurring in cells, especially those which are drug resistant, have not been studied thoroughly. This study presents response of wild and drug resistant breast cancer cells to classical photodynamic therapy with Photofrin or experimental photodynamic therapy with cyanine IR-775, combined with electroporation.

Photodynamic reaction or electroporation alone had no cytotoxic effect, but their combination significantly disturbed cellular functions. Applying electroporation allowed the drugs to increase its accumulation, especially for a poorly permeant cyanine in drug resistant cells. FACS analysis showed that even at relatively mild electric field, ca. 90% of cells were permeabilized. High intracellular concentration of drugs triggered the cellular defense system through increased expression of glutathione S-transferase and multidrug resistance proteins (MDR1 and MRP7), particularly in drug resistant cells. Finally, expressively decreased cell metabolism and proliferation, as well as formation of apoptotic bodies and fragmentation of cells were observed after the combined treatment.

The results show that electroporation can be used for effective delivery of photosensitizers, even to drug resistant breast cancer cells, which was not tested before. This shows that electro-photodynamic treatment could be a promising approach to overcome a problem of drug resistance in cancer cells.



中文翻译:

光动力治疗联合电透化对野生型和耐药性乳腺癌细胞的生物学作用

电化学疗法已成为肿瘤学中成功使用的治疗方案之一。然而,尚未彻底研究细胞中发生的生物学效应,尤其是对药物具有抗性的生物学效应。这项研究提出了野生和耐药性乳腺癌细胞对Photofrin的经典光动力疗法或花菁IR-775与电穿孔结合的实验性光动力疗法的反应。

单独的光动力反应或电穿孔没有细胞毒性作用,但是它们的组合显着干扰了细胞功能。进行电穿孔可使药物增加其积累,特别是对于耐药性细胞中花青渗透性较差的情况。FACS分析表明,即使在相对温和的电场下,约。90%的细胞被透化。细胞内高浓度药物尤其是在耐药细胞中,通过增加谷胱甘肽S-转移酶和多药耐药蛋白(MDR1和MRP7)的表达来触发细胞防御系统。最后,在联合处理后,观察到表达的细胞代谢和增殖减少,以及凋亡小体的形成和细胞的碎裂。

结果表明,电穿孔可以用于有效地递送光敏剂,甚至可以递送至耐药性乳腺癌细胞,而以前从未进行过测试。这表明电光动力学治疗可能是克服癌细胞耐药性的一种有前途的方法。

更新日期:2018-04-19
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