Faculty of Medicine, Department of Medical Biology, Kocaeli University, Kocaeli, Turkey.
Faculty of Medicine, Department of Histology and Embryology, Sakarya University, Korucuk, Sakarya, 54290, Turkey.
Mol Biol Rep. 2024 Jan 18;51(1):145. doi: 10.1007/s11033-023-09055-3.
The topoisomerase I inhibitor topotecan (TPT) is used in the treatment of recurrent small cell lung cancer (SCLC). However, the drug has a limited success rate and causes distress to patients due to its side effects, such as hematologic toxicities, including anemia and thrombocytopenia. Due to these pharmacokinetic limitations and undesirable side effects of chemotherapeutic drugs, the development of combination therapies has gained popularity in SCLC. Meclofenamic acid (MA), a nonsteroidal anti-inflammatory drug, has demonstrated anticancer effects on various types of cancers through different mechanisms. This study aims to investigate the potential synergistic effects of MA and TPT on the small cell lung cancer cell line DMS114.
To assess the cytotoxic and apoptotic effects of the combined treatment of MA and TPT, trypan blue exclusion assay, Annexin V, acridine orange/propidium iodide staining, western blot, and cell cycle analysis were conducted. The results demonstrated that the combination of MA and TPT elicited synergistic effects by enhancing toxicity in DMS114 cells (P < 0.01) without causing toxicity in healthy epithelial lung cells MRC5. The strongest synergistic effect was observed when the cells were treated with 60 µM MA and 10 nM TPT for 48 h (CI = 0,751; DRI = 10,871).
This study, for the first time, furnishes compelling evidence that MA and TPT synergistically reduce cellular proliferation and induce apoptosis in SCLC cells. Combinations of these drugs holds promise as a potential therapeutic strategy to improve efficacy and reduce the side effects associated with TPT.
拓扑异构酶 I 抑制剂托泊替康（TPT）用于治疗复发性小细胞肺癌（SCLC）。然而，由于其副作用，如血液学毒性，包括贫血和血小板减少症，该药物的成功率有限，并给患者带来不适。由于这些药代动力学限制和化疗药物的不良副作用，联合治疗在 SCLC 中越来越受欢迎。非甾体抗炎药甲氯芬酸（MA）通过不同机制对各种类型的癌症表现出抗癌作用。本研究旨在研究 MA 和 TPT 对小细胞肺癌细胞系 DMS114 的潜在协同作用。
为了评估 MA 和 TPT 联合治疗的细胞毒性和细胞凋亡作用，进行了台盼蓝排除试验、Annexin V、吖啶橙/碘化丙啶染色、western blot 和细胞周期分析。结果表明，MA 和 TPT 的联合治疗通过增强 DMS114 细胞的毒性（P<0.01）而没有引起健康上皮肺细胞 MRC5 的毒性，从而产生协同作用。当细胞用 60µM MA 和 10nM TPT 处理 48 小时时，观察到最强的协同作用（CI=0.751；DRI=10.871）。
本研究首次提供了令人信服的证据，表明 MA 和 TPT 协同减少 SCLC 细胞的细胞增殖并诱导细胞凋亡。这些药物的联合使用有望成为一种潜在的治疗策略，以提高疗效并减少与 TPT 相关的副作用。
