| 姚伟龙,罗晓雅,焦 月,丛 雪,刘雨琪.BET抑制剂JQ1通过调控GSK3对结肠癌细胞HCT116增殖及凋亡的影响[J].,2023,(7):1201-1205 |
| BET抑制剂JQ1通过调控GSK3对结肠癌细胞HCT116增殖及凋亡的影响 |
| Effect of BET Inhibitor JQ1 on Proliferation and Apoptosis of Colon Cancer Cell HCT116 by Regulating GSK3 |
| 投稿时间：2022-11-24 修订日期：2022-12-20 |
| DOI：10.13241/j.cnki.pmb.2023.07.001 |
| 中文关键词: BET抑制剂JQ1 GSK3 结肠癌 HCT116细胞 增殖 凋亡 |
| 英文关键词: BET inhibitor JQ1 GSK3 Colon cancer HCT116 cells Proliferation Apoptosis |
| 基金项目:国家自然科学基金青年基金项目（81703534）；北京友谊医院科研启动基金资助项目（yyqdkt2020-33）；首都医学科研培育基金项目（PYZ21062） |
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| 中文摘要: |
| 摘要 目的：探讨BET抑制剂JQ1通过调控GSK3对结肠癌细胞HCT116增殖及凋亡的影响。方法：将HCT116细胞进行培养，按处理方式的不同分为对照组（NC组）、给药组（JQ1组）、给药+沉默组（JQ1+siRNA-GSK3组）与给药+过表达组（JQ1+OE-GSK3组）。分别通过细胞增殖-毒性检测（CCK-8）实验检测细胞增殖情况；原位末端标记（TUNEL）染色观察细胞凋亡水平；流式细胞术检测细胞凋亡数量；逆转录-聚合酶链反应（RT-PCR）检测相关mRNA含量水平表达变化；蛋白质印迹法（Western Blot）检测增殖与凋亡相关蛋白表达情况。结果：与NC组表现出的高增殖活性相比，给予JQ1后能够明显抑制HCT116细胞的增殖活性（P<0.05）；与JQ1组相比，沉默GSK3后其增殖活性则进一步下降，过表达GSK3后其增殖活性明显上升（P<0.05）。TUNEL染色结果显示，对NC组相比，JQ1组及JQ1+siRNA-GSK3组细胞凋亡水平显著上升；与JQ1组相比，过表达GSK3后其凋亡水平明显降低（P<0.05）。流式细胞术结果显示，NC组细胞凋亡数量最少，而给予JQ1后凋亡细胞数量显著增加，同时沉默GSK3后其细胞凋亡数量进一步上升，过表达GSK3后细胞凋亡数量明显下降（P<0.05）。Western Blot与RT-PCR显示；与NC组相比，给予JQ1及siRNA-GSK3处理后Caspase-3及BAX表达显著增加，GSK3与PCNA表达显著降低（P<0.05）；与JQ1组相比，过表达GSK3后Caspase-3及BAX表达明显降低，GSK3与PCNA表达明显上调（P<0.05）。结论：JQ1能够抑制HCT116细胞的增殖水平并促进其凋亡，从而发挥抗肿瘤作用，这一过程可能与JQ1能够抑制GSK3的表达有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of BET inhibitor JQ1 on the proliferation and apoptosis of colon cancer cell HCT116 by regulating GSK3. Methods: HCT116 cells were cultured and divided into control group(NC group),administration group(JQ1 group), administration+silence group(JQ1+ siRNA-GSK3 group) and administration + overexpression group (JQ1+OE-GSK3 group) according to different treatment methods. Cell proliferation activity was detected by Cell Counting Kit-8(CCK-8) technique. The apoptosis level was observed by TdT-mediated nick end labeling(TUNEL) staining; Detection of apoptosis by flow cytometry. Reverse Transcription-Polymerase Chain Reaction(RT-PCR) was used to detect the changes of related mRNA levels.Western Blot was used to detect the expression of proteins related to proliferation and apoptosis. Results: Compared with the high proliferation activity of NC group, the proliferation activity of HCT116 cells was significantly inhibited after JQ1 treatment(P<0.05). Compared with JQ1 group, the proliferation activity of HCT116 cells was further decreased after GSK3 silencing,and significantly increased after GSK3 overexpression(P<0.05).TUNEL staining results showed that compared with NC group, the apoptosis level of JQ1 group and JQ1+ siRNA-GSK3 group was significantly increased, and the apoptosis level of GSK3 overexpressed group was significantly decreased compared with JQ1 group(P<0.05). Flow cytometry results showed that the number of apoptotic cells in NC group was the least, while the number of apoptotic cells was significantly increased after JQ1 treatment, and the number of apoptotic cells was further increased after GSK3 silencing, and significantly decreased after GSK3 overexpression(P<0.05).Western Blot and RT-PCR showed that compared with NC group, the expressions of Caspase-3 and BAX were significantly increased after treatment with JQ1 and siRNA-GSK3, while the expressions of GSK3 and PCNA were significantly decreased (P<0.05). Compared with JQ1 group, the expressions of Caspase-3 and BAX were significantly decreased after GSK3 overexpression, and the expressions of GSK3 and PCNA were significantly up-regulated(P<0.05). Conclusion: JQ1 can inhibit HCT116 proliferation, promote apoptosis, thus exerting anti-tumor effect, which may be related to the inhibition of GSK3 expression by JQ1. |
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