Feng Tao, Hu Guofang, Luo Yinjun, Zhang Xin, Chen Hong, Liang Zuoren, He Xianjiao, Ma Shijing, Wei Jinting, Fang Xiaoyan, Li Biao, Wang Jinhua, Liao Suchan
School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China.
Graduate School, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China.
Biol Pharm Bull. 2025;48(7):1096-1106. doi: 10.1248/bpb.b25-00053.
Nasopharyngeal carcinoma (NPC) is a highly invasive form of head and neck cancer that arises from nasopharyngeal epithelial cells. Celastrol and curcumin, both derived from traditional Chinese medicine, have demonstrated antitumor potential. However, the clinical application of these compounds is limited by their low bioavailability and/or toxicity. Cancer cell viability, apoptosis, autophagy, ferroptosis, and mitochondrial fission- and fusion-related proteins were evaluated following treatment with celastrol alone, curcumin alone, and their combination. The results indicated that low doses of celastrol (0.7 μM) alone do not inhibit proliferation in NPC cells. However, when combined with curcumin, there is a significant enhancement of the antiproliferative effect. There was no significant alteration in the expression levels of the apoptosis-related proteins BCL2-associated X and cleaved caspase 3 in either the curcumin alone or the combined treatment groups compared to the control group. Interestingly, the combined treatment significantly increased the ferroptosis contributor acyl-CoA synthetase long-chain family member 4 while notably decreasing solute carrier family 7 member 11 and glutathione peroxidase 4, accompanied by increased phosphorylation of dynamin-related protein 1. Furthermore, the combined treatment exhibited significant antitumor efficacy with low toxic side effects in a xenograft model. In conclusion, our study provides new insights into combination therapies to enhance anti-NPC efficacy.
鼻咽癌（NPC）是一种起源于鼻咽上皮细胞的高度侵袭性头颈部癌症。来源于中药的雷公藤红素和姜黄素已显示出抗肿瘤潜力。然而，这些化合物的临床应用受到其低生物利用度和/或毒性的限制。在用雷公藤红素单独处理、姜黄素单独处理及其组合处理后，评估癌细胞活力、凋亡、自噬、铁死亡以及线粒体裂变和融合相关蛋白。结果表明，低剂量的雷公藤红素（0.7 μM）单独处理不抑制NPC细胞的增殖。然而，当与姜黄素联合使用时，抗增殖作用显著增强。与对照组相比，单独使用姜黄素或联合治疗组中凋亡相关蛋白BCL2相关X和裂解的半胱天冬酶3的表达水平均无显著变化。有趣的是，联合治疗显著增加了铁死亡促进因子酰基辅酶A合成酶长链家族成员4，同时显著降低溶质载体家族7成员11和谷胱甘肽过氧化物酶4，并伴有动力相关蛋白1磷酸化增加。此外，联合治疗在异种移植模型中显示出显著的抗肿瘤疗效且毒副作用低。总之，我们的研究为增强抗鼻咽癌疗效的联合治疗提供了新的见解。
