Department of Oncology, Poznan University of Medical Sciences, Szamarzewskiego 82/84, 60-569 Poznań, Poland.
Department of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, Poland.
Biomed Pharmacother. 2022 Jun;150:113036. doi: 10.1016/j.biopha.2022.113036. Epub 2022 Apr 27.
Inherent or developed during treatment drug resistance is the main reason for the low effectiveness of chemotherapy in ovarian cancer. IFI16 is a cytoplasmic/nuclear protein involved in response to virus's infection and cell cycle arrest associated with the cellular senescence.
Here we performed a detailed IFI16 expression analysis in ovarian cancer cell lines sensitive (A2780) and resistant to doxorubicin (DOX) (A2780DR1 and A2780DR2) and paclitaxel (PAC) (A2780PR1). IFI16 mRNA level, protein level in the nuclear and cytoplasmic fraction (Western blot analysis), the protein expression in cancer cells and nuclei (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were performed in this study.
We observed upregulation of IFI16 expression in drug resistant cell lines with dominant cytoplasmic localization in DOX-resistant cell lines and nuclear one in the PAC-resistant cell line. The most abundantly overexpressed isoforms of IFI16 were IFI16A and IFI16C. Finally, an analysis of a histological type of ovarian cancer (immunohistochemistry) showed expression in serous ovarian cancer.
Expression of IFI16 in drug-resistant cell lines suggests its role in drug resistance development in ovarian cancer. Expression in serous ovarian cancer suggests its role in the pathogenesis of this histological type.
在治疗过程中产生或固有药物耐药性是卵巢癌化疗效果不佳的主要原因。IFI16 是一种细胞质/核蛋白，参与病毒感染的反应和与细胞衰老相关的细胞周期停滞。
在这里，我们对卵巢癌细胞系（A2780）对阿霉素（DOX）（A2780DR1 和 A2780DR2）和紫杉醇（PAC）（A2780PR1）敏感和耐药的 IFI16 表达进行了详细分析。在这项研究中，我们进行了 IFI16mRNA 水平、核和细胞质部分的蛋白水平（Western blot 分析）、癌细胞和细胞核中的蛋白表达（免疫荧光分析）以及癌症患者病变（免疫组化）的分析。
我们观察到耐药细胞系中 IFI16 表达上调，在 DOX 耐药细胞系中主要定位于细胞质，在 PAC 耐药细胞系中定位于核。IFI16 过表达最丰富的亚型是 IFI16A 和 IFI16C。最后，对卵巢癌的组织学类型（免疫组化）进行分析显示，在浆液性卵巢癌中表达。
耐药细胞系中 IFI16 的表达表明其在卵巢癌耐药发展中的作用。在浆液性卵巢癌中的表达表明其在这种组织学类型发病机制中的作用。
