PDF(Pubmed)
Abstract：
UNASSIGNED: Chronic or recurrent inflammatory injury to the intestinal mucosa is closely related to inflammation-related colorectal cancer (CRC). This study aimed to examine the protective effects of palbociclib, a stimulator of interferon genes (STING) antagonist, on colitis-related colorectal carcinogenesis.
UNASSIGNED: Bioinformatic analyses, including Gene Ontology (GO) enrichment, gene set enrichment analysis (GSEA), and network analysis, were conducted. Male C57BL/6 mice were administered azoxymethane (AOM) and dextran sulfate sodium (DSS), followed by treatment with palbociclib for 6 weeks. The general conditions of mice were observed and recorded. The colon histopathology was assessed based on hematoxylin and eosin (H&E) staining results. Relative messenger RNA (mRNA) expression levels of interferon b1 (Ifnb1), interleukin 6 (Il6), and interleukin 1b (Il1b) in colon were estimated based on quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis.
UNASSIGNED: The STING signaling pathway was significantly upregulated in stages III and IV of CRC in The Cancer Genome Atlas (TCGA)-CRC cohort. After treatment with AOM/DSS, the weight of mice decreased significantly, whereas administration of palbociclib partially reversed this trend. The mouse colon treated with AOM/DSS showed significant pathological damages, disorderly epithelial cell structure, atypical hyperplasia, and infiltration of several inflammatory cell types; however, the colon damage was remarkably reduced upon treatment with palbociclib. It was also found that palbociclib almost abolished the increase in the downstream effectors of STING-mediated transcription in the colon tissue treated with AOM/DSS, as evidenced by the transcription levels of Ifnb1, Il6, and Il1b.
UNASSIGNED: These findings indicate that the STING pathway is closely associated with CRC. Palbociclib significantly alleviates tumor development in AOM/DSS-induced colitis-associated CRC.
UNASSIGNED: Bioinformatic analyses, including Gene Ontology (GO) enrichment, gene set enrichment analysis (GSEA), and network analysis, were conducted. Male C57BL/6 mice were administered azoxymethane (AOM) and dextran sulfate sodium (DSS), followed by treatment with palbociclib for 6 weeks. The general conditions of mice were observed and recorded. The colon histopathology was assessed based on hematoxylin and eosin (H&E) staining results. Relative messenger RNA (mRNA) expression levels of interferon b1 (Ifnb1), interleukin 6 (Il6), and interleukin 1b (Il1b) in colon were estimated based on quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis.
UNASSIGNED: The STING signaling pathway was significantly upregulated in stages III and IV of CRC in The Cancer Genome Atlas (TCGA)-CRC cohort. After treatment with AOM/DSS, the weight of mice decreased significantly, whereas administration of palbociclib partially reversed this trend. The mouse colon treated with AOM/DSS showed significant pathological damages, disorderly epithelial cell structure, atypical hyperplasia, and infiltration of several inflammatory cell types; however, the colon damage was remarkably reduced upon treatment with palbociclib. It was also found that palbociclib almost abolished the increase in the downstream effectors of STING-mediated transcription in the colon tissue treated with AOM/DSS, as evidenced by the transcription levels of Ifnb1, Il6, and Il1b.
UNASSIGNED: These findings indicate that the STING pathway is closely associated with CRC. Palbociclib significantly alleviates tumor development in AOM/DSS-induced colitis-associated CRC.
摘要：
■肠粘膜的慢性或复发性炎症损伤与炎症相关性结直肠癌（CRC）密切相关。本研究旨在研究palbociclib的保护作用，干扰素基因（STING）拮抗剂的刺激物，关于结肠炎相关的结直肠癌的发生。
■生物信息学分析，包括基因本体论(GO)富集，基因集富集分析(GSEA)，和网络分析，进行了。雄性C57BL/6小鼠给予氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS），随后用palbociclib治疗6周。观察并记录小鼠的一般情况。基于苏木精和曙红(H&E)染色结果评估结肠组织病理学。干扰素b1（Ifnb1）的相对信使RNA（mRNA）表达水平，白细胞介素6（Il6），根据定量实时逆转录聚合酶链反应（qRT-PCR）分析，估计结肠中的白细胞介素1b（Il1b）。
■在癌症基因组图谱（TCGA）-CRC队列中，STING信号通路在CRC的III和IV期显著上调。用AOM/DSS处理后，小鼠的体重明显下降，而palbociclib的给药部分逆转了这一趋势.经AOM/DSS处理的小鼠结肠表现出显著的病理损伤,无序的上皮细胞结构，不典型增生,和几种炎症细胞类型的浸润;然而，palbociclib治疗后，结肠损伤明显减轻。还发现palbociclib几乎消除了用AOM/DSS处理的结肠组织中STING介导的转录的下游效应子的增加，Ifnb1、Il6和Il1b的转录水平证明了这一点。
■这些发现表明STING途径与CRC密切相关。Palbociclib可显着缓解AOM/DSS诱导的结肠炎相关性CRC中的肿瘤发展。
■生物信息学分析，包括基因本体论(GO)富集，基因集富集分析(GSEA)，和网络分析，进行了。雄性C57BL/6小鼠给予氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS），随后用palbociclib治疗6周。观察并记录小鼠的一般情况。基于苏木精和曙红(H&E)染色结果评估结肠组织病理学。干扰素b1（Ifnb1）的相对信使RNA（mRNA）表达水平，白细胞介素6（Il6），根据定量实时逆转录聚合酶链反应（qRT-PCR）分析，估计结肠中的白细胞介素1b（Il1b）。
■在癌症基因组图谱（TCGA）-CRC队列中，STING信号通路在CRC的III和IV期显著上调。用AOM/DSS处理后，小鼠的体重明显下降，而palbociclib的给药部分逆转了这一趋势.经AOM/DSS处理的小鼠结肠表现出显著的病理损伤,无序的上皮细胞结构，不典型增生,和几种炎症细胞类型的浸润;然而，palbociclib治疗后，结肠损伤明显减轻。还发现palbociclib几乎消除了用AOM/DSS处理的结肠组织中STING介导的转录的下游效应子的增加，Ifnb1、Il6和Il1b的转录水平证明了这一点。
■这些发现表明STING途径与CRC密切相关。Palbociclib可显着缓解AOM/DSS诱导的结肠炎相关性CRC中的肿瘤发展。
