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Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer

  • Authors:
    • Sujuan Li
    • Sen Wang
    • Anping Zhang
    • Lixia Luo
    • Jie Song
    • Guoli Wei
    • Zhijun Fang
  • View Affiliations / Copyright

    Affiliations: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 37
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    Published online on: February 20, 2024
       https://doi.org/10.3892/ijo.2024.5625
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Abstract

The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX‑induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the Cucurbitaceae family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. In vivo anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and in vivo anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high‑mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid‑derived suppressor cells, T regulatory cells and M2‑polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.
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Copy and paste a formatted citation
Spandidos Publications style
Li S, Wang S, Zhang A, Luo L, Song J, Wei G and Fang Z: Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer. Int J Oncol 64: 37, 2024.
APA
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., & Fang, Z. (2024). Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer. International Journal of Oncology, 64, 37. https://doi.org/10.3892/ijo.2024.5625
MLA
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., Fang, Z."Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer". International Journal of Oncology 64.4 (2024): 37.
Chicago
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., Fang, Z."Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer". International Journal of Oncology 64, no. 4 (2024): 37. https://doi.org/10.3892/ijo.2024.5625
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Wang S, Zhang A, Luo L, Song J, Wei G and Fang Z: Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer. Int J Oncol 64: 37, 2024.
APA
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., & Fang, Z. (2024). Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer. International Journal of Oncology, 64, 37. https://doi.org/10.3892/ijo.2024.5625
MLA
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., Fang, Z."Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer". International Journal of Oncology 64.4 (2024): 37.
Chicago
Li, S., Wang, S., Zhang, A., Luo, L., Song, J., Wei, G., Fang, Z."Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer". International Journal of Oncology 64, no. 4 (2024): 37. https://doi.org/10.3892/ijo.2024.5625
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