Xi Yunzhu, Zeng Saili, Tan Xiaowu, Deng Xiaoyu
Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421000, P.R. China.
Int J Oncol. 2025 Mar;66(3). doi: 10.3892/ijo.2025.5727. Epub 2025 Feb 14.
Non‑small cell lung cancer (NSCLC) is a malignant tumor of significant clinical relevance. Curcumin has been investigated for its potential anticancer properties, as it has been reported to act through multiple cancer‑related targets and pathways. The present study aimed to explore the effects of curcumin in NSCLC using both and models. NSCLC cell lines (specifically, A549 and NCI‑H1299 cells), and a mouse tumor model established through the subcutaneous injection of A549 cells, were utilized to evaluate the effects of curcumin intervention. The effects of treatment with curcumin on NOD‑like receptor pyrin domain‑containing 3 (NLRP3) ubiquitination, cell pyroptosis and pyroptosis‑associated factors were also evaluated. In addition, Smad ubiquitination regulatory factor 2 (Smurf2) was analyzed via a series of knockdown and overexpression experiments, both and , aimed at investigating its association with curcumin and NLRP3. The results obtained from these experiments showed that curcumin inhibited NSCLC cell growth, promoted pyroptosis and reduced the level of NLRP3 ubiquitination. NLRP3 knockdown reversed the curcumin‑induced increase in pyroptosis‑associated factors both and . Additionally, Smurf2 interacted with NLRP3 and alterations in Smurf2 expression levels influenced NLRP3 ubiquitination and cell pyroptosis. Moreover, molecular docking analysis demonstrated that curcumin could bind directly to Smurf2, which subsequently led to an inhibition of Smurf2 activity. Knockdown of Smurf2 enhanced curcumin's ability to stabilize NLRP3 and to promote pyroptosis, whereas Smurf2 overexpression negated these effects. In the animal model, curcumin treatment led to reduced tumor volumes and weights, in addition to a decreased expression level of Ki67 and increased expression levels of NLRP3 and pyroptosis‑associated factors. Similarly, these effects were enhanced or reversed by Smurf2 knockdown or overexpression, respectively. In conclusion, the findings of the present study showed that curcumin inhibited Smurf2 activity, thereby promoting NLRP3‑dependent pyroptosis in NSCLC cells. In addition, these findings have provided mechanistic insights into the role of curcumin in NSCLC, opening an avenue for its potential therapeutic application.
非小细胞肺癌（NSCLC）是一种具有重要临床意义的恶性肿瘤。姜黄素因其潜在的抗癌特性而受到研究，据报道它可通过多个与癌症相关的靶点和途径发挥作用。本研究旨在使用细胞和动物模型探索姜黄素在非小细胞肺癌中的作用。利用非小细胞肺癌细胞系（具体为A549和NCI-H1299细胞）以及通过皮下注射A549细胞建立的小鼠肿瘤模型来评估姜黄素干预的效果。还评估了姜黄素处理对含NOD样受体吡咯结构域3（NLRP3）泛素化、细胞焦亡及焦亡相关因子的影响。此外，通过一系列体内和体外的敲低和过表达实验分析了Smad泛素化调节因子2（Smurf2），旨在研究其与姜黄素和NLRP3的关联。这些实验结果表明，姜黄素抑制非小细胞肺癌细胞生长，促进焦亡并降低NLRP3泛素化水平。NLRP3敲低逆转了姜黄素诱导的体内和体外焦亡相关因子的增加。此外，Smurf2与NLRP3相互作用，Smurf2表达水平的改变影响NLRP3泛素化和细胞焦亡。而且，分子对接分析表明姜黄素可直接与Smurf2结合，随后导致Smurf2活性受到抑制。敲低Smurf2增强了姜黄素稳定NLRP3和促进焦亡的能力，而Smurf2过表达则消除了这些作用。在动物模型中，姜黄素处理导致肿瘤体积和重量减小，此外Ki67表达水平降低，NLRP3和焦亡相关因子表达水平升高。同样，这些作用分别通过Smurf2敲低或过表达得到增强或逆转。总之，本研究结果表明姜黄素抑制Smurf2活性，从而促进非小细胞肺癌细胞中依赖NLRP3的焦亡。此外，这些发现为姜黄素在非小细胞肺癌中的作用提供了机制性见解，为其潜在的治疗应用开辟了一条途径。
