Induction of apoptosis by oridonin in nonfunctioning pituitary adenoma cells

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-08-26 DOI:10.1002/ddr.22251
Hui-Tong Chen, Xing-Yi Yuan, Zhong-Yu Wang, Dong Fan, Xiong-Ming Luo, Jun-Hua Yang, Yu-Xin Ma, Jing Liu, Xin Wang, Zong-Ming Wang
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Abstract

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay, 5‑Ethynyl‑2'‑deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.

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奥利多宁诱导无功能垂体腺瘤细胞凋亡
无功能垂体腺瘤(NFPA)是垂体腺瘤(PA)的主要亚型之一,其主要治疗方法是手术切除。然而,普通手术无法完全切除病灶,仍缺乏一线治疗手段,因此开发治疗 NFPA 的新药无疑迫在眉睫。据报道,奥利多宁(ORI)对多种肿瘤都有抗肿瘤作用,但它对 NFPA 是否也有同样的作用,还有待进一步研究。研究人员采用细胞计数试剂盒-8、集落形成试验、5-乙炔基-2'-脱氧尿苷增殖试验、伤口愈合试验和Transwell试验检测了ORI对垂体衍生滤泡细胞系(PDFS)的细胞活力、集落形成、增殖能力、迁移和侵袭的影响。通过转录组测序分析筛选对照组和 ORI 处理组的差异表达基因,并通过京都基因组百科全书(KEGG)和基因本体(GO)富集进行分析。细胞周期分析用于检测细胞周期的变化。通过Annexin V-异硫氰酸荧光素/碘化丙啶染色检测ORI处理细胞的凋亡情况。用 Western 印迹法检测 Bax、Bcl-2 和裂解 Caspase-3 蛋白的表达。ORI抑制了PDFS细胞的活力,并显著抑制了细胞的增殖、迁移和侵袭。GO和KEGG结果显示,ORI与PDFS细胞的细胞周期和细胞凋亡等信号通路有关。此外,ORI 还能阻滞 PDFS 细胞进入 G2/M 期,并诱导细胞凋亡。ORI能协同触发PDFS细胞的细胞周期中断和细胞凋亡,使其成为一种治疗NFPA的有效药物。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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