Background/Objectives: In the fight against ovarian cancer, various therapies have been employed, with a strong focus on developing novel derivatives of existing substances. Methods: In this study, we continue our research on novel xanthone derivatives in combination with mild hyperthermia, targeting ovarian cancer cell lines TOV-21G and SK-OV-3. Using qPCR arrays, we analyzed 84 cellular stress-related genes categorized into anti-oxidant and pro-oxidant enzymes, molecular chaperones, and xenobiotic metabolism including the cytochrome P450 group. Furthermore, we conducted in silico analyses to investigate the pathways of the most affected genes, gene set enrichment, and gene ontology. Results: The most significant changes were observed in SOD2, SOD3, CYP2F1, CYP1B1, and HMOX1. Additional changes related to drug toxicity and the postulated mechanism of action were also identified. Based on in silico analyses, we concluded that the primary node of hyperthermia-induced changes is HSPA1A. Heat-induced alterations predominantly revolve around misfolded proteins, monooxygenase activity, and ATPase activity. Conclusions: To summarize, the combined therapy of novel xanthone derivatives and mild hyperthermia shows promising results and warrants further investigation to fully elucidate the mechanisms of action underlying these effects.
背景/目的：在抗击卵巢癌的过程中，多种疗法已被应用，其中重点聚焦于开发现有物质的新型衍生物。方法：本研究继续探索新型呫吨酮衍生物联合温和热疗对卵巢癌细胞系TOV-21G和SK-OV-3的作用机制。通过qPCR阵列技术，我们分析了84个细胞应激相关基因，这些基因分为抗氧化酶、促氧化酶、分子伴侣以及异生物质代谢（包括细胞色素P450家族）等类别。此外，我们通过计算机模拟分析研究了受影响最显著基因的通路、基因集富集及基因本体功能。结果：SOD2、SOD3、CYP2F1、CYP1B1和HMOX1基因表现出最显著的变化，同时发现了与药物毒性及推测作用机制相关的其他变化。基于计算机模拟分析，我们得出结论：热疗诱导变化的核心节点是HSPA1A基因。热诱导的改变主要围绕错误折叠蛋白、单加氧酶活性和ATP酶活性展开。结论：综上所述，新型呫吨酮衍生物联合温和热疗的协同疗法展现出良好前景，值得进一步深入研究以全面阐明其作用机制。
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