Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR), contributing to aggressive metastatic disease. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me), a glycyrrhetinic acid derivative, reportedly improves the therapeutic response to erlotinib (ERL), an EGFR tyrosine kinase inhibitor. In the present study, we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R (ERL-resistant) cells to ERL. Herein, we first established the selectivity of ERL-induced drug resistance in the HCC827R cells, which was sensitized when ERL was combined with CDODA-Me (2 μM), shifting the IC₅₀ from 23.48 μM to 5.46 μM. Subsequently, whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44% of the whole transcriptome (WT)) and 174 upregulated genes (0.36% of the WT), of which approximately 80% were unique to the ERL + CDODA-Me group. Synergistic effects centered on losses to cell cycle progression transcripts, a reduction of minichromosome maintenance complex components (MCM2-7), all key components of the Cdc45·MCM2-7GINS (CMG) complex, and replicative helicases; these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress, including sulfiredoxin 1, heme oxygenase 1, and stress-induced growth inhibitor 1. Collectively, these findings indicate that the synergistic therapeutic effects of ERL + CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.

非小细胞肺癌 (NSCLC) 通常以表皮生长因子受体 (EGFR) 的潜在突变为特征，导致侵袭性转移性疾病。Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me)，一种甘草次酸衍生物，据报道可改善对厄洛替尼 (ERL) 的治疗反应，厄洛替尼 (ERL) 是一种 EGFR 酪氨酸激酶抑制剂。在本研究中，我们进行了一系列研究来证明 CDODA-Me (2 μM) 在使 HCC827R（ERL 抗性）细胞对 ERL 敏感方面的功效。在此，我们首先确定了 HCC827R 细胞中 ERL 诱导的耐药性的选择性，当 ERL 与 CDODA-Me (2 μM) 结合时，HCC827R 细胞变得敏感，改变了 IC ₅₀从 23.48 μM 到 5.46 μM。随后，全转录组微阵列表达数据表明，ERL + CDODA-Me 的组合引发了 210 个下调基因（占全转录组（WT）的 0.44%）和 174 个上调基因（占 WT 的 0.36%），其中约 80% 是ERL + CDODA-Me 组独有。协同效应集中在细胞周期进程转录本的损失、微染色体维护复合物成分 (MCM2-7)、Cdc45·MCM2-7GINS (CMG) 复合物的所有关键成分和复制解旋酶的减少；这些影响等同于上调与核因子红细胞 2 相关的过程，如 2 对氧化应激的翻译反应，包括硫氧还蛋白 1、血红素加氧酶 1 和应激诱导的生长抑制剂 1。总的来说，