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Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mutated p53 gene.

Abstract

To increase the chemo-sensitivity of anaplastic thyroid carcinoma, we examined the effects of glycerol on the tumor growth after CDDP treatment. The cultured cells of an anaplastic thyroid carcinoma cell line (8305c) carrying a mutated p53 gene (mp53) were transplanted into the thighs of nude mice. Tumor growth was evaluated until 24 days after intraperitoneal injection of CDDP and/or pre-injection of glycerol to the tumor. We treated the mice with half the tumor volume of glycerol (1.2 M) and/or CDDP at 6 mg/kg (BW) either of which hardly inhibited tumor growth by itself. When we treated the mice with the combination of glycerol and CDDP at these concentrations, however, a clear delay of the tumor growth was observed. We also immunohistochemically analyzed the effects of glycerol on the induction of caspase-3 activity and apoptosis. Cells positive for cleavage to active caspase-3 and 85 kDa PARP, and apoptosis were hardly observed in the tumors when they were treated with glycerol or CDDP alone. In contrast, when they were treated with CDDP combined with glycerol, such positive cells were significantly increased. It has been shown that glycerol synergistically enhanced the effects of CDDP as a tumor suppressive agent through the induction of caspase-3-mediated apoptosis in 8305c tumors. Therefore, glycerol might be useful for chemotherapy in patients with mp53 cancer cells.

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  • Authors+Show Affiliations

    ,

    Department of Otorhinolaryngology, Nara Medical University, Kashihara, Nara 634-8521, Japan.

    , , , , , , ,

    Source

    Oncology reports 11:4 2004 Apr pg 821-4

    MeSH

    Animals
    Antineoplastic Combined Chemotherapy Protocols
    Apoptosis
    Carcinoma
    Caspase 3
    Caspases
    Cell Culture Techniques
    Cisplatin
    Drug Synergism
    Genes, p53
    Glycerol
    Humans
    Immunohistochemistry
    Male
    Mice
    Mice, Inbred BALB C
    Models, Animal
    Neoplasm Transplantation
    Point Mutation
    Thyroid Neoplasms

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15010879

    Citation

    Yuki, Kazue, et al. "Glycerol Enhances CDDP-induced Growth Inhibition of Thyroid Anaplastic Carcinoma Tumor Carrying Mutated P53 Gene." Oncology Reports, vol. 11, no. 4, 2004, pp. 821-4.
    Yuki K, Takahashi A, Ota I, et al. Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mutated p53 gene. Oncol Rep. 2004;11(4):821-4.
    Yuki, K., Takahashi, A., Ota, I., Ohnishi, K., Yasumoto, J., Kanata, H., ... Ohnishi, T. (2004). Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mutated p53 gene. Oncology Reports, 11(4), pp. 821-4.
    Yuki K, et al. Glycerol Enhances CDDP-induced Growth Inhibition of Thyroid Anaplastic Carcinoma Tumor Carrying Mutated P53 Gene. Oncol Rep. 2004;11(4):821-4. PubMed PMID: 15010879.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Glycerol enhances CDDP-induced growth inhibition of thyroid anaplastic carcinoma tumor carrying mutated p53 gene. AU - Yuki,Kazue, AU - Takahashi,Akihisa, AU - Ota,Ichiro, AU - Ohnishi,Ken, AU - Yasumoto,Jun-Ichi, AU - Kanata,Hirokazu, AU - Yane,Katsunari, AU - Hosoi,Hiroshi, AU - Ohnishi,Takeo, PY - 2004/3/11/pubmed PY - 2004/12/16/medline PY - 2004/3/11/entrez SP - 821 EP - 4 JF - Oncology reports JO - Oncol. Rep. VL - 11 IS - 4 N2 - To increase the chemo-sensitivity of anaplastic thyroid carcinoma, we examined the effects of glycerol on the tumor growth after CDDP treatment. The cultured cells of an anaplastic thyroid carcinoma cell line (8305c) carrying a mutated p53 gene (mp53) were transplanted into the thighs of nude mice. Tumor growth was evaluated until 24 days after intraperitoneal injection of CDDP and/or pre-injection of glycerol to the tumor. We treated the mice with half the tumor volume of glycerol (1.2 M) and/or CDDP at 6 mg/kg (BW) either of which hardly inhibited tumor growth by itself. When we treated the mice with the combination of glycerol and CDDP at these concentrations, however, a clear delay of the tumor growth was observed. We also immunohistochemically analyzed the effects of glycerol on the induction of caspase-3 activity and apoptosis. Cells positive for cleavage to active caspase-3 and 85 kDa PARP, and apoptosis were hardly observed in the tumors when they were treated with glycerol or CDDP alone. In contrast, when they were treated with CDDP combined with glycerol, such positive cells were significantly increased. It has been shown that glycerol synergistically enhanced the effects of CDDP as a tumor suppressive agent through the induction of caspase-3-mediated apoptosis in 8305c tumors. Therefore, glycerol might be useful for chemotherapy in patients with mp53 cancer cells. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/15010879/Glycerol_enhances_CDDP_induced_growth_inhibition_of_thyroid_anaplastic_carcinoma_tumor_carrying_mutated_p53_gene_ L2 - http://www.spandidos-publications.com/or/11/4/821 DB - PRIME DP - Unbound Medicine ER -