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合成姜黄素类似物:通过 NF-κB 通路抑制人喉癌细胞的侵袭、血管生成和转移。

Synthetic curcumin analog: inhibiting the invasion, angiogenesis, and metastasis in human laryngeal carcinoma cells via NF-kB pathway.

机构信息

Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, 605 014, India.

出版信息

Mol Biol Rep. 2021 Aug;48(8):6065-6074. doi: 10.1007/s11033-021-06610-8. Epub 2021 Aug 5.

DOI:10.1007/s11033-021-06610-8
PMID:34355287
Abstract

BACKGROUND

Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC), induces 1% of all cancer deaths. Curcumin the active constituent of turmeric, is shown to be effective in the treatment of various cancers. In the present study, we explored the mechanistic role of bis-demethoxy curcumin analog (BDMC-A) as a chemotherapeutic agent. We investigated its inhibitory effect on invasion, angiogenesis, and metastasis in human laryngeal carcinoma (Hep-2) cells in comparison with curcumin.

METHODS

The effect of curcumin and BDMC-A on transcription factors (NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ, β-catenin, COX-2, MMP-9, VEGF, TIMP-2) involved in signal transduction cascade, invasion, and angiogenesis in Hep-2 cells were quantified using Western blotting and RT-PCR technique. ELISA was used to measure the pro-inflammatory markers in Hep-2 cells treated with curcumin and BDMC-A.

RESULTS

The results showed that BDMC-A inhibits the transcription factors NF-κB, p65, c-Jun, c-Fos, STAT3, STAT5, PPAR-γ and β-catenin, which are responsible for tumor progression and malignancy. Moreover, BDMC-A treatment downregulated MMP-9, VEGF, TGF- β, IL-6 and IL-8 and upregulated TIMP-2 levels. The effects were more significant compared to curcumin.

CONCLUSION

Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.

摘要

背景

喉癌是头颈部鳞状细胞癌(HNSCC)中最常见的一种,导致 1%的癌症死亡。姜黄素是姜黄的活性成分,已被证明可有效治疗各种癌症。在本研究中,我们探讨了双去甲氧基姜黄素类似物(BDMC-A)作为化疗药物的作用机制。与姜黄素相比,我们研究了其对人喉癌细胞(Hep-2)侵袭、血管生成和转移的抑制作用。

方法

使用 Western blot 和 RT-PCR 技术定量测定姜黄素和 BDMC-A 对参与信号转导级联、侵袭和血管生成的转录因子(NF-κB、p65、c-Jun、c-Fos、STAT3、STAT5、PPAR-γ、β-catenin、COX-2、MMP-9、VEGF、TIMP-2)的影响。使用 ELISA 测定姜黄素和 BDMC-A 处理的 Hep-2 细胞中的促炎标志物。

结果

结果表明,BDMC-A 抑制转录因子 NF-κB、p65、c-Jun、c-Fos、STAT3、STAT5、PPAR-γ 和β-catenin,这些因子负责肿瘤的进展和恶性转化。此外,BDMC-A 治疗下调 MMP-9、VEGF、TGF-β、IL-6 和 IL-8 并上调 TIMP-2 水平。与姜黄素相比,效果更为显著。

结论

我们的综合结果表明,BDMC-A 比姜黄素更有效地抑制了侵袭、血管生成和转移的标志物。

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