Cisplatin-based therapy is a widely used chemotherapeutic regimen for non-small cell lung cancer (NSCLC); however, drug resistance limits its efficacy. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive compound from frankincense, has been shown to exert anti-cancer effects. The aim of this study is to explore the potential of AKBA in combination with cisplatin as a new regimen for NSCLC. CCK8 assay and clone formation assay were used to determine the effects of AKBA in combination with cisplatin on cell viability of NSCLC cell lines. A three-dimensional spherification assay was used to simulate in vivo tumor formation. Flow cytometry was performed to examine cell cycle distribution and the percentages of apoptotic cells. The associated proteins and mRNA of cell cycle, apoptosis, and autophagy were measured by western blotting and real-time fluorescence quantitative PCR. Immunofluorescence assay was used to test apoptotic nuclei and autolysosome. Small interfering RNA experiments were used to silence the expression of p21. Combination treatment of AKBA and cisplatin inhibited cell viability, clone formation, and three-dimensional spherification, enhanced G₀/G₁ phase arrest, increased the percentages of apoptotic cells, and decreased the ratio of positive autolysosomes, compared with cisplatin alone. AKBA in combination with cisplatin suppressed the protein expressions of cyclin A2, cyclin E1, p-cdc2, CDK4, Bcl-xl, Atg5, and LC3A/B, and upregulated p27 and p21 mRNA levels in A549 cells. Downregulation of p21 decreased G₀/G₁ phase arrest and the percentages of apoptotic cells, and promoted autophagy in NSCLC A549 cells. Our study demonstrates that AKBA enhances the cisplatin sensitivity of NSCLC cells and that the mechanisms involve G₀/G₁ phase arrest, apoptosis induction, and autophagy suppression via targeting p21-dependent signaling pathway.

以顺铂为基础的治疗是一种广泛使用的非小细胞肺癌 (NSCLC) 化疗方案；然而，耐药性限制了其功效。Acetyl-11-keto-β-boswellic acid (AKBA) 是一种来自乳香的生物活性化合物，已被证明具有抗癌作用。本研究的目的是探索 AKBA 联合顺铂作为 NSCLC 新方案的潜力。CCK8测定和克隆形成测定用于确定AKBA与顺铂联合对NSCLC细胞系的细胞活力的影响。三维球化试验用于模拟体内肿瘤形成。进行流式细胞术以检查细胞周期分布和凋亡细胞的百分比。细胞周期、细胞凋亡、通过蛋白质印迹和实时荧光定量PCR测量和自噬。免疫荧光法用于检测凋亡细胞核和自溶酶体。使用小干扰 RNA 实验来沉默 p21 的表达。AKBA 和顺铂联合处理抑制细胞活力、克隆形成和三维球化，增强 G₀ /G ₁期阻滞，与单独使用顺铂相比，增加了凋亡细胞的百分比，并降低了阳性自溶酶体的比例。AKBA 与顺铂联合抑制细胞周期蛋白 A2、细胞周期蛋白 E1、p-cdc2、CDK4、Bcl-xl、Atg5 和 LC3A/B 的蛋白质表达，并上调 A549 细胞中 p27 和 p21 mRNA 水平。p21 的下调降低了 G ₀ /G ₁期阻滞和凋亡细胞的百分比，并促进了非小细胞肺癌 A549 细胞的自噬。我们的研究表明，AKBA 增强了 NSCLC 细胞对顺铂的敏感性，其机制涉及 G ₀ /G ₁期阻滞、凋亡诱导和通过靶向 p21 依赖性信号通路抑制自噬。