Wyciszkiewicz Aleksandra, Lach Michal S, Wróblewska Joanna P, Michalak Marcin, Suchorska Wiktoria M, Kalinowska Alicja, Michalak Slawomir
Department of Neurology, Division of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland.
Radiobiology Laboratory, Greater Poland Cancer Centre, Garbary 15, 61-866 Poznań, Poland.
EXCLI J. 2021 May 25;20:935-947. doi: 10.17179/excli2021-3706. eCollection 2021.
Ovarian cancer is the most deadly gynecologic malignancy worldwide. Although the primary response to chemotherapy is high, the majority of patients will develop resistance against applied treatment. In this study, we focused on resistance to cisplatin, a first-line drug used for the treatment of ovarian cancer. The mechanism of the resistance development process is widely described, but there is a lack of information about the involvement of members of small heat shock proteins (HSPs) and their transport via exosomes. In this study, we used two cell lines: A2780 and SKOV3, and their cisplatin-resistance variants: A2780 CDDP and SKOV3 CDDP. We have shown that the expression of three small HSPs (HSPB5, HSPB6, and HSPB8) in cisplatin-resistant cell lines differs from their sensitive counterparts. Further, we isolated exosomes and determined the small HSPs in their cargo. In A2780 WT we observed a low amount of HSPB5 and HSPB6. We did not observe the expression of small HSPs in the SKOV3 cell line in both sensitive and resistant variants. Our data suggest the involvement of small HSPs in drug resistance of ovarian cancer and their presence is not related to exosomal transport. Analysis of the biological consequences of the imbalance of small HSPs expression in cisplatin resistance needs further investigation.
卵巢癌是全球最致命的妇科恶性肿瘤。尽管对化疗的初始反应率较高，但大多数患者会对所用治疗产生耐药性。在本研究中，我们聚焦于对顺铂的耐药性，顺铂是用于治疗卵巢癌的一线药物。耐药性发展过程的机制已有广泛描述，但关于小热休克蛋白（HSPs）成员的参与及其通过外泌体的转运情况却缺乏相关信息。在本研究中，我们使用了两种细胞系：A2780和SKOV3，以及它们的顺铂耐药变体：A2780 CDDP和SKOV3 CDDP。我们已经表明，顺铂耐药细胞系中三种小热休克蛋白（HSPB5、HSPB6和HSPB8）的表达与其敏感对应物不同。此外，我们分离了外泌体并测定了其中的小热休克蛋白。在A2780野生型中，我们观察到HSPB5和HSPB6的含量较低。在SKOV3细胞系的敏感和耐药变体中，我们均未观察到小热休克蛋白的表达。我们的数据表明小热休克蛋白参与了卵巢癌的耐药性，且它们的存在与外泌体转运无关。顺铂耐药中小热休克蛋白表达失衡的生物学后果分析需要进一步研究。
