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Article

Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma

  • Authors:
    • Ryo Tsukada
    • Motonari Nomura
    • Takehisa Ueno
    • Hiroomi Okuyama
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan
  • Article Number: 79
    |
    Published online on: February 22, 2022
       https://doi.org/10.3892/or.2022.8290
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Abstract

Cellular inhibitor of apoptosis protein‑1 (cIAP1) is a key regulator of programmed cell death and is known to be associated with chemotherapeutic resistance. The present study aimed to investigate the antitumor efficacy of birinapant, a novel selective inhibitor of cIAP1, against cisplatin (CDDP)‑resistant hepatoblastoma (HB) cells. Western blot analysis was used to investigate the antitumor effect of birinapant on cIAP1 expression in Huh6 cells at the protein level. A WST‑8 assay was performed to evaluate the tumor growth inhibitory effect of birinapant on the human HB cell lines, Huh6 and HepG2. Huh6 cells were exposed to CDDP and/or birinapant in order to confirm tumor growth inhibition. The antitumor efficacy of birinapant plus CDDP combination therapy was significantly higher than that of CDDP monotherapy in a dose‑dependent manner (P=0.035). The study also investigated the antitumor efficacy of birinapant plus CDDP combination therapy in an established xenograft model of SCID mice. Compared with CDDP monotherapy, birinapant combined with CDDP showed better inhibition of tumor growth (P=0.121). It was observed that the mRNA expression of cIAP1 in tumors was significantly enriched in the CDDP monotherapy group compared with that in the untreated group. Furthermore, immunohistochemical staining was performed to compare cIAP1 expression in pre‑ and post‑chemotherapy specimens in patients with HB, and a significant increase was observed in the post‑chemotherapy specimens (P<0.001). CDDP‑resistant Huh6 (Huh6‑CDDPR) cells were also established following repeated exposure to CDDP. Birinapant was substantially more effective against the Huh6‑CDDPR cells than against the Huh6 wild‑type cells. Taken together, these findings suggest that repeated exposure to CDDP enhances cIAP1 expression in HB cells and that birinapant is a promising therapeutic drug for CDDP‑resistant HB.
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Copy and paste a formatted citation
Spandidos Publications style
Tsukada R, Nomura M, Ueno T and Okuyama H: Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma. Oncol Rep 47: 79, 2022.
APA
Tsukada, R., Nomura, M., Ueno, T., & Okuyama, H. (2022). Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma. Oncology Reports, 47, 79. https://doi.org/10.3892/or.2022.8290
MLA
Tsukada, R., Nomura, M., Ueno, T., Okuyama, H."Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma". Oncology Reports 47.4 (2022): 79.
Chicago
Tsukada, R., Nomura, M., Ueno, T., Okuyama, H."Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma". Oncology Reports 47, no. 4 (2022): 79. https://doi.org/10.3892/or.2022.8290
Copy and paste a formatted citation
x
Spandidos Publications style
Tsukada R, Nomura M, Ueno T and Okuyama H: Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma. Oncol Rep 47: 79, 2022.
APA
Tsukada, R., Nomura, M., Ueno, T., & Okuyama, H. (2022). Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma. Oncology Reports, 47, 79. https://doi.org/10.3892/or.2022.8290
MLA
Tsukada, R., Nomura, M., Ueno, T., Okuyama, H."Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma". Oncology Reports 47.4 (2022): 79.
Chicago
Tsukada, R., Nomura, M., Ueno, T., Okuyama, H."Inhibition of cIAP1 in the effective suppression of chemotherapy‑resistant hepatoblastoma". Oncology Reports 47, no. 4 (2022): 79. https://doi.org/10.3892/or.2022.8290
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