文章：

亚甲基蓝代谢疗法抑制体内卵巢肿瘤生长

Methylene Blue Metabolic Therapy Restrains In Vivo Ovarian Tumor Growth

原文发布日期：13 January 2024

DOI: 10.3390/cancers16020355

类型: Article

开放获取: 是

英文摘要：

Ovarian cancer remains a significant challenge, especially in platinum-resistant cases where treatment options are limited. In this study, we investigated the potential of methylene blue (MB) as a metabolic therapy and complementary treatment approach for ovarian cancer. Our findings demonstrated a significant in vivo reduction in the proliferation of TOV112D-based ovarian-cell-line xenografts. In this preclinical study, which used a carboplatin-resistant ovarian cancer tumor model implanted into mice, MB-mediated metabolic therapy exhibited superior tumor slowdown compared to carboplatin treatment alone. This indicates, for the first time, MB’s potential as an alternative or adjuvant treatment, especially for resistant cases. Our in vitro study on TOV112D and ARPE-19 sheds light on the impact of such an MB-based metabolic therapy on mitochondrial energetics (respiration and membrane potential). MB showed a modulatory role in the oxygen consumption rate and the mitochondrial membrane potential. These results revealed, for the first time, that MB specifically targets TOV112D mitochondria and probably induces cell apoptosis. The differential response of normal (ARPE-19) and cancer (TOV112D) cells to the MB treatment suggests potential alterations in cancer cell mitochondria, opening avenues for therapeutic approaches that target the mitochondria. Overall, our findings suggest the efficacy of MB as a possible treatment for ovarian cancer and provide valuable insights into the mechanisms underlying the efficacy of methylene blue metabolic therapy in ovarian cancer treatment.

摘要翻译： 

卵巢癌治疗仍面临重大挑战，尤其在铂类耐药病例中治疗方案极为有限。本研究探讨了亚甲蓝（MB）作为代谢疗法及卵巢癌辅助治疗手段的潜力。实验结果显示，基于TOV112D卵巢细胞系的异种移植瘤在体内增殖显著受抑。在卡铂耐药卵巢癌小鼠模型的临床前研究中，MB介导的代谢疗法比单用卡铂治疗表现出更优越的肿瘤生长抑制作用。这首次揭示了MB作为替代或辅助治疗方案的潜力，尤其适用于耐药病例。通过对TOV112D和ARPE-19细胞的体外研究，我们阐明了MB代谢疗法对线粒体能量代谢（呼吸作用和膜电位）的影响。MB对耗氧率和线粒体膜电位具有调节作用，首次证实其特异性靶向TOV112D细胞线粒体并可能诱导细胞凋亡。正常细胞（ARPE-19）与癌细胞（TOV112D）对MB治疗的差异性反应，提示癌细胞线粒体可能存在特异性改变，这为开发靶向线粒体的治疗策略开辟了新途径。总体而言，本研究证实了MB作为卵巢癌潜在治疗手段的有效性，并为理解亚甲蓝代谢疗法在卵巢癌治疗中的作用机制提供了重要依据。

原文链接：

Methylene Blue Metabolic Therapy Restrains In Vivo Ovarian Tumor Growth