Borzdziłowska Paulina, Bednarek Ilona
Department of Biotechnology and Genetic Engineering, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.
Biomedicines. 2022 May 11;10(5):1116. doi: 10.3390/biomedicines10051116.
Ovarian cancer is one of the cancers that, unfortunately, is detected at a late stage of development. The current use of treatment has many side effects. Notably, up to 20% of patients show cisplatin resistance. We assess the effects of cisplatin and/or α-mangostin, a natural plant derivative, on ovarian cancer cells and on the cancer cell microenvironment. The effect of cisplatin and/or α-mangostin on the following cells of ovarian cancer lines: A2780, TOV-21G, and SKOV-3 was verified using the XTT cytotoxicity assay. The separate and combined effects of tested drugs on ovarian cancer cell viability were assessed. We assessed the influence of chemotherapeutic agents on the possibility of modulating the microenvironment. For this purpose, we isolated exosomes from drug-treated and untreated ovarian cancer cells. We estimated the differences in the amounts of exosomes released from cancer cells (NTA technique). We also examined the effects of isolated exosome fractions on normal human cells (NHDF human fibroblast line). In the present study, we demonstrate that treatment of A2780, SKOV-3, and TOV-21G cells with α-mangostin in combination with cisplatin can allow a reduction in cisplatin concentration while maintaining the same cytotoxic effect. Ovarian cancer cells release a variable number of exosomes into the microenvironment when exposed to α-mangostin and/or cisplatin. However, it is important to note that the cargo carried by exosomes released from drug-treated cells may be significantly different.
卵巢癌是一种不幸在发展晚期才被发现的癌症。目前的治疗方法有许多副作用。值得注意的是，高达20%的患者表现出顺铂耐药性。我们评估顺铂和/或天然植物衍生物α-山竹素对卵巢癌细胞和癌细胞微环境的影响。使用XTT细胞毒性试验验证了顺铂和/或α-山竹素对以下卵巢癌细胞系：A2780、TOV-21G和SKOV-3细胞的作用。评估了受试药物对卵巢癌细胞活力的单独和联合作用。我们评估了化疗药物对调节微环境可能性的影响。为此，我们从经药物处理和未经处理的卵巢癌细胞中分离外泌体。我们估计了癌细胞释放的外泌体数量差异（纳米颗粒跟踪分析技术）。我们还检测了分离的外泌体组分对正常人细胞（NHDF人成纤维细胞系）的影响。在本研究中，我们证明用α-山竹素联合顺铂处理A2780、SKOV-3和TOV-21G细胞可以在保持相同细胞毒性作用的同时降低顺铂浓度。当暴露于α-山竹素和/或顺铂时，卵巢癌细胞会向微环境中释放数量不等的外泌体。然而，需要注意的是，经药物处理的细胞释放的外泌体所携带的货物可能有显著差异。
