Tianjin Medical Journal

Tianjin Medical Journal ›› 2025, Vol. 53 ›› Issue (5): 449-455.doi: 10.11958/20250340

• Cell and Molecular Biology •     Next Articles

Mechanism study of benzyl isothiocyanate combined with sorafenib in the treatment of anaplastic thyroid cancer

MA Chunmei1,2(), YU Peng3, ZHANG Qicheng4, YANG Lei5, LI Dihua5, TAN Jian1, MENG Zhaowei1,△()   

  1. 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin 300052, China
    2 Imaging Center
    3 Department of Nuclear Medicine, North China University of Science and Technology Affiliated Hospital
    4 Tianjin Medical University General Hospital, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute
    5 Tianjin Nankai Hospital, Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases
  • Received:2025-01-22 Revised:2025-03-13 Published:2025-05-15 Online:2025-05-28
  • Contact: △ E-mail：zmeng@tmu.edu.cn

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Abstract:

Objective To investigate the mechanism of benzyl isothiocyanate (BITC) combined with sorafenib (Sor) in the treatment of anaplastic thyroid cancer (ATC). Methods Two ATC cell lines, 8505C and CAL-62, were treated with Sor at concentrations of 0, 20, 30, 40, and 50 μmol/L. The cell survival rate was assessed using CCK-8 assay. The combined dose of BITC and Sor was determined by calculating combination index (CI). CAL-62 and 8505C cells were exposed to 10 μmol/L BITC (BITC group), 10 μmol/L Sor (Sor group), or a combination of 10 μmol/L BITC and 10 μmol/L Sor (BITC+Sor group) for 24 hours. The control group was not treated. The effects of Sor and BITC on ATC cell viability were evaluated using the CCK-8 method. Apoptosis was analyzed via flow cytometry. Western blot assay was employed to detect the protein expression levels of LC3B Ⅱ, Beclin-1 and nuclear factor (NF)-κB. Real-time fluorescence quantitative PCR was used to quantify the mRNA levels of LC3B. Additionally, CAL-62 cells were subcutaneously injected into mice to establish tumor xenograft model. Mice were treated with BITC (100 mg/kg, intraperitoneal injection), Sor (30 mg/kg, intragastric administration) or a combination of BITC and Sor every other day for 21 days. Finally, the expression levels of LC3B Ⅱ, Beclin-1 and NF-κB in tumor tissue were analyzed by Western blot assay. Results Sor significantly inhibited the viability of CAL-62 and 8505C cells in a concentration-dependent manner. The combination index (CI) was 0.710 at BITC 10 μmol/L and Sor 10 μmol/L, indicating a moderate synergistic effect between the two drugs. In both 8505C and CAL-62 cells, compared with the control group, treatment with BITC or Sor resulted in the decreased cell viability, as well as reduced expression levels of Beclin-1 and NF-κB proteins (P<0.05), and the apoptosis rate, LC3B mRNA and LC3B Ⅱ protein expression levels were significantly increased (P<0.05). When BITC and Sor were combined, the cell viability, Beclin-1 and NF-κB protein expressions were further reduced compared to either drug alone, while the apoptosis rate, LC3B mRNA and LC3B Ⅱ protein expression levels were significantly elevated (P<0.05). In the mouse xenograft tumor model, the BITC+Sor group exhibited increased LC3B Ⅱ expression, along with decreased Beclin-1 and NF-κB expression levels, tumor volume and tumor mass compared to the BITC or Sor groups (P<0.05). Conclusion The combination of BITC and Sor can inhibit ATC cells through NF-κB pathway, induce autophagy and promote apoptosis in vitro and in vivo.

Key words: thyroid carcinoma, anaplastic, sorafenib, autophagy, NF-kappa B, benzyl isothiocyanate

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