Chun Jaemoo
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Int J Mol Sci. 2023 Aug 3;24(15):12397. doi: 10.3390/ijms241512397.
Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer cells, the increased reliance of cisplatin-resistant cells on glycolysis has gained increasing attention. Isoalantolactone, a sesquiterpene lactone isolated from L., possesses various pharmacological properties, including anticancer activity. In this study, isoalantolactone was investigated as a potential glycolysis inhibitor to overcome cisplatin resistance in OC. Isoalantolactone effectively targeted key glycolytic enzymes (e.g., lactate dehydrogenase A, phosphofructokinase liver type, and hexokinase 2), reducing glucose consumption and lactate production in cisplatin-resistant OC cells (specifically A2780 and SNU-8). Importantly, it also sensitized these cells to cisplatin-induced apoptosis. Isoalantolactone-cisplatin treatment regulated mitogen-activated protein kinase and AKT pathways more effectively in cisplatin-resistant cells than individual treatments. In vivo studies using cisplatin-sensitive and resistant OC xenograft models revealed that isoalantolactone, either alone or in combination with cisplatin, significantly suppressed tumor growth in cisplatin-resistant tumors. These findings highlight the potential of isoalantolactone as a novel glycolysis inhibitor for treating cisplatin-resistant OC. By targeting the dysregulated glycolytic pathway, isoalantolactone offers a promising approach to overcoming drug resistance and enhancing the efficacy of cisplatin-based therapies.
顺铂是一种用于治疗卵巢癌（OC）的强效化疗药物。然而，由于顺铂耐药性的产生，其疗效受到显著限制。尽管获得顺铂耐药性是一个复杂的过程，涉及癌细胞内各种分子改变，但顺铂耐药细胞对糖酵解的依赖性增加已日益受到关注。异土木香内酯是一种从[植物名称未给出]中分离出的倍半萜内酯，具有多种药理特性，包括抗癌活性。在本研究中，研究了异土木香内酯作为一种潜在的糖酵解抑制剂来克服OC中的顺铂耐药性。异土木香内酯有效地靶向关键糖酵解酶（如乳酸脱氢酶A、肝型磷酸果糖激酶和己糖激酶2），减少顺铂耐药OC细胞（特别是A2780和SNU - 8）中的葡萄糖消耗和乳酸生成。重要的是，它还使这些细胞对顺铂诱导的凋亡敏感。与单独治疗相比，异土木香内酯 - 顺铂联合治疗在顺铂耐药细胞中更有效地调节丝裂原活化蛋白激酶和AKT通路。使用顺铂敏感和耐药OC异种移植模型的体内研究表明，异土木香内酯单独或与顺铂联合使用，均能显著抑制顺铂耐药肿瘤的生长。这些发现突出了异土木香内酯作为一种新型糖酵解抑制剂治疗顺铂耐药OC的潜力。通过靶向失调的糖酵解途径，异土木香内酯为克服耐药性和提高基于顺铂的治疗疗效提供了一种有前景的方法。
