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查尔酮 9X 通过降低 FOXM1 表达抑制体外神经胶质瘤细胞生长和迁移并诱导细胞凋亡,抑制体内肿瘤生长。

Chalcone 9X Contributed to Repressing Glioma Cell Growth and Migration and Inducing Cell Apoptosis by Reducing FOXM1 Expression In Vitro and Repressing Tumor Growth In Vivo.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.

出版信息

Biomed Res Int. 2022 Aug 8;2022:8638085. doi: 10.1155/2022/8638085. eCollection 2022.

Abstract

OBJECTIVE

Natural and synthetic chalcones played roles in inflammation and cancers. Chalcone 9X was an aromatic ketone that was found to inhibit cell growth of hepatic cancer and lung cancer cells. In this study, we wanted to investigate the functions of Chalcone 9X in glioma.

MATERIALS AND METHODS

Chemical Chalcone 9X was added in human glioma cell lines (U87 and T98G cells) and normal astrocyte cell lines (HA1800) with various concentrations (0 mol/L, 20 mol/L, 50 mol/L, and 100 mol/L). CCK-8 assay was used to measure cell viability. Flow cytometric assay was used to measure cell apoptotic rates. Wound healing assay and transwell assay were used to measure cell invasion. RT-PCR was used to detect relative mRNA expressions, and the protein expressions were detected by western blot (WB) and immunohistochemical staining (IHC). Finally, nude mouse xenograft assay was performed to prove the effects of Chalcone 9X in vivo.

RESULTS

Results revealed that Chalcone 9X treatment suppressed cell viability and cell migration capacity; it could also induce cell apoptosis in U87 and T98G cells with dose dependence. However, it had little cytotoxicity to normal astrocyte HA1800 cells. Moreover, Chalcone 9X treatment could repress the mRNA and protein expressions of FOXM1 in human glioma cell lines, which was an oncogene that could promote the progression and malignancy of glioma. In addition, FOXM1 overexpression dismissed the Chalcone 9X effects on cell proliferation, apoptosis, and migration in human glioma cell lines. Finally, in vivo assay showed that Chalcone 9X treatment repressed the expression of FOXM1, which inhibited the tumor growth of a xenograft model injected with U87 in nude mice.

CONCLUSIONS

In all, we found that Chalcone 9X could suppress cell proliferation and migration and induce cell apoptosis in human glioma cells, while it has little cytotoxicity to normal astrocyte cells. Therefore, we uncovered a novel way that Chalcone 9X could inhibit FOXM1 expression and repress the progression and biofunctions of glioma cells, which might be a potential therapeutic drug for treating human glioma.

摘要

目的

天然和合成查耳酮在炎症和癌症中发挥作用。查耳酮 9X 是一种芳香酮,已被发现可抑制肝癌和肺癌细胞的生长。在这项研究中,我们想研究查耳酮 9X 在神经胶质瘤中的作用。

材料和方法

用不同浓度(0mol/L、20mol/L、50mol/L 和 100mol/L)的化学查耳酮 9X 处理人神经胶质瘤细胞系(U87 和 T98G 细胞)和正常星形胶质细胞系(HA1800)。CCK-8 测定法用于测量细胞活力。流式细胞术测定法用于测量细胞凋亡率。划痕愈合试验和 Transwell 试验用于测量细胞侵袭。RT-PCR 用于检测相对 mRNA 表达,Western blot(WB)和免疫组织化学染色(IHC)用于检测蛋白表达。最后,进行裸鼠异种移植试验以证明查耳酮 9X 的体内作用。

结果

结果表明,查耳酮 9X 处理抑制了 U87 和 T98G 细胞的细胞活力和迁移能力;它还可以在剂量依赖性诱导细胞凋亡。然而,它对正常星形胶质细胞 HA1800 细胞几乎没有细胞毒性。此外,查耳酮 9X 处理可以抑制人神经胶质瘤细胞系中 FOXM1 的 mRNA 和蛋白表达,FOXM1 是一种可以促进神经胶质瘤进展和恶性转化的癌基因。此外,FOXM1 过表达消除了查耳酮 9X 对人神经胶质瘤细胞系中细胞增殖、凋亡和迁移的作用。最后,体内试验表明,查耳酮 9X 处理抑制了 FOXM1 的表达,从而抑制了裸鼠注射 U87 的异种移植模型中的肿瘤生长。

结论

总之,我们发现查耳酮 9X 可以抑制人神经胶质瘤细胞的增殖和迁移,并诱导细胞凋亡,而对正常星形胶质细胞几乎没有细胞毒性。因此,我们发现了一种新的途径,即查耳酮 9X 可以抑制 FOXM1 的表达并抑制神经胶质瘤细胞的进展和生物功能,这可能是治疗人类神经胶质瘤的一种潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/9377910/0f08f0f540a1/BMRI2022-8638085.001.jpg

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