2024 年第 5 期 第 19 卷

益气活血解毒方治疗铂类耐药卵巢癌患者的作用机制探究

Study on the mechanism of Yiqi Huoxue Jiedu decoction in the treatment of patients with platinum-resistant ovarian cancer

作者：吴晓晴 卢雯平

英文作者：Wu Xiaoqing Lu Wenping

单位：中国中医科学院广安门医院肿瘤科，北京100053

英文单位：Department of Oncology Guang′anmen Hospital Chinese Academy of Chinese Medical Sciences Beijing 100053 China

关键词：卵巢癌；转录组测序；铂类耐药；益气活血解毒方

英文关键词：Ovariancancer;Transcriptomesequencing;Platinumresistance;YiqiHuoxueJiedudecoction

• 摘要：

• 目的  探究益气活血解毒方治疗铂类耐药卵巢癌（PROC）患者的作用机制。方法  选取2022年9月至2023年3月就诊于中国中医科学院广安门医院肿瘤科门诊的PROC患者12例，根据治疗方式不同，将患者分为中医组和对照组，各6例。对照组接受医师选择的方案，中医组在接受医师选择的方案的基础上接受益气活血解毒方治疗。采集外周血，提取外周血中RNA，质控合格后逆转录并纯化cDNA，使用Illumina测序平台进行转录组测序，使用DESeq2软件筛选2组的差异长链非编码RNA（lncRNA）和差异表达基因（DEG），使用顺式调控的方式预测lncRNA作用的靶基因，将预测靶基因与测序DEG结果取交集，得出重要靶基因和调控它们的lncRNA，进行基因本体论、京都基因与基因组百科全书和蛋白质相互作用网络（PPI）分析。结果  溶质运载家族3成员2（SLC3A2）、BCL2样蛋白11（BCL2L11）是可能由益气活血解毒方调控的重要靶基因，它们由lncRNA SNHG1、MIR4435-2HG、AC108463.3调控。益气活血解毒方调控的DEG在细胞代谢、细胞自噬、蛋白-DNA结合功能中富集。血管内皮生长因子受体信号通路、凋亡、自噬、癌症中胆碱代谢、哺乳动物雷帕霉素靶蛋白信号通路中富集。PPI发现益气活血解毒方以调控具有凋亡、细胞代谢、DNA修复功能的蛋白为主，以及经典的致癌蛋白肉瘤基因、丝裂原活化蛋白激酶3等。结论  益气活血解毒方治疗PROC患者的靶点是由lncRNA SNHG1、MIR4435-2HG、AC108463.3调控的SLC3A2、BCL2L11，从而调控了癌细胞的程序性死亡等生物学行为和癌症的经典通路。

• Objective  To explore the mechanism of Yiqi Huoxue Jiedu decoction in the treatment of platinum-resistant ovarian cancer (PROC). Methods  A total of 12 patients with PROC in the Department of Oncology, Guang′anmen Hospital, China Academy of Chinese Medical Sciences from September 2022 to March 2023 were selected. According to different treatment methods, the patients were divided into traditional Chinese medicine group and control group, with 6 cases in each group. The control group was treated with the regimen selected by the doctor, and the traditional Chinese medicine group was treated with the Yiqi Huoxue Jiedu decoction on the basis of the regimen selected by the doctor. Peripheral blood was collected, RNA was extracted from peripheral blood, reverse transcribed and cDNA was purified after qualified quality control, and transcriptome sequencing was performed using Illumina sequencing platform. DESeq2 software was used to screen differential long-chain non-coding RNA (lncRNA) and differential expression gene (DEG) between the two groups.The target genes of lncRNA were predicted by cis-regulation, and the results of predicted target genes and sequenced DEG were intercrossed to obtain important target genes and lncrnas regulating them. Gene ontology, Kyoto Encyclopedia of Genes and Genomes and protein interaction network (PPI) analyses were performed. Results  Solute carrier family 3 member 2 (SLC3A2) and BCL2-like protein 11 (BCL2L11) were the important target genes regulated by Yiqi Huoxue Jiedu decoction, and they were regulated by lncRNA SNHG1, MIR4435-2HG and AC108463.3.The DEG regulated by Yiqi Huoxue Jiedu decoction was enriched in the functions of cell metabolism, cell autophagy and protein-DNA binding. Vascular endothelial growth factor receptor signaling pathway, apoptosis, autophagy, choline metabolism in cancer, and mammalian target of rapamycin signaling pathway were enriched. PPI showed that Yiqi Huoxue Jiedu decoction mainly regulated proteins with apoptosis, cell metabolism, DNA repair function, as well as classic oncogene sarcoma gene, mitogen-activated protein kinase 3, etc. Conclusion  The targets of Yiqi Huoxue Jiedu decoction in the treatment of PROC patients are SLC3A2 and BCL2L11 regulated by lncRNA SNHG1, MIR4435-2HG and AC108463.3, thereby regulating the biological behavior of cancer cells such as programmed cell death and the classical pathway of cancer.