Mechanism of benzyl isothiocyanate in the treatment of undifferentiated thyroid cancer
10.3760/cma.j.cn311282-20240225-00077
- VernacularTitle:异硫氰酸苄酯治疗未分化甲状腺癌的机制研究
- Author:
Chunmei MA
1
;
Duo HAN
;
Huiying ZHANG
;
Lei YANG
;
Dihua LI
;
Qicheng ZHANG
;
Yan WANG
;
Ke XU
;
Qiang JIA
;
Wei ZHENG
;
Jian TAN
;
Zhaowei MENG
Author Information
1. 天津医科大学总医院核医学科，天津市功能影像重点实验室和天津市影像医学研究所，天津 300052
- Keywords:
Benzyl isothiocyanate;
Anaplastic thyroid cancer;
Autophagy;
nuclear factor κB signaling pathway;
Apoptosis
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(11):966-977
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.
