Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Fujin Road 1266, Changchun 130021, China.
Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Xiantai Street 126, Changchun 130033, China.
Molecules. 2023 Jul 29;28(15):5746. doi: 10.3390/molecules28155746.
Lung cancer seriously threatens human health. To explore the molecular mechanism of 20(S)-Protopanaxadiol (PPD) on human non-small cell lung cancer cells, we investigated the transcriptional profile of PPD-treated NCI-H1299 cells. Cell proliferation, cell cycle, and apoptosis were detected using cell counting kit-8 and flow cytometry, respectively. Differentially expressed genes (DEGs) between PPD-treated and untreated cells were determined using RNA sequencing and bioinformatic analysis. Protein phosphorylation was detected using Western blotting. Data of mRNA expression profiles of lung cancer were from The Cancer Genome Atlas (TCGA) and analyzed using R software version 4.3.1. PPD showed an inhibitory effect on the proliferation of NCI-H1299 cells and induced apoptosis. There were 938 upregulated genes and 466 downregulated genes in PPD-treated cells, and DEGs were primarily enriched in the MAPK signaling pathway. The detection of phosphorylation revealed that the phosphorylation of ERK and p38 MAPK was significantly reduced in PPD-treated cells. Further comparison of PPD-regulated DEGs with clinical data of lung adenocarcinoma demonstrated that most downregulated genes in tumor tissues were upregulated in PPD-treated cells or vice versa. Two PPD-downregulated genes and were associated with patients' overall survival. Therefore, PPD could inhibit NCI-H1299 cells by affecting gene expression and regulating ERK and p38 MAPK pathways.
肺癌严重威胁人类健康。为了探索 20(S)-原人参二醇 (PPD) 对人非小细胞肺癌细胞的分子机制，我们研究了 PPD 处理的 NCI-H1299 细胞的转录谱。使用细胞计数试剂盒-8 和流式细胞术分别检测细胞增殖、细胞周期和细胞凋亡。使用 RNA 测序和生物信息学分析确定 PPD 处理和未处理细胞之间的差异表达基因 (DEGs)。使用 Western blot 检测蛋白磷酸化。肺癌 mRNA 表达谱数据来自癌症基因组图谱 (TCGA)，并使用 R 软件版本 4.3.1 进行分析。PPD 对 NCI-H1299 细胞的增殖有抑制作用，并诱导细胞凋亡。PPD 处理细胞中有 938 个上调基因和 466 个下调基因，DEGs 主要富集在 MAPK 信号通路中。磷酸化检测显示，PPD 处理细胞中 ERK 和 p38 MAPK 的磷酸化明显降低。进一步将 PPD 调节的 DEGs 与肺腺癌的临床数据进行比较表明，肿瘤组织中大多数下调基因在 PPD 处理的细胞中上调，反之亦然。两个 PPD 下调基因 和 与患者的总生存时间有关。因此，PPD 可能通过影响基因表达并调节 ERK 和 p38 MAPK 通路来抑制 NCI-H1299 细胞。
