Changes of 31P-MR Spectroscopy in Experimental Tumors Following Radiotherapy Compined with 5-Fluorouracil Compound(UFT).

Ohkubo, Masaki

doi:10.1620/tjem.169.215

Cited by 4 publications

(1 citation statement)

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“…In this study, we observed that indomethacin treatment suppressed the growth of all tumors examined. We compared the inhibitory effect of indomethacin on tumor growth with the reported inhibitory effects of other chemotherapeutic agents: the maximal reduction of 55% in Colon-26 tumor size of our study is comparable with the antitumor effect of cisplatin, 17) as well as the antitumor effect of 5-fluorouracil alone in Meth-A tumor-bearing mice, 18) and the maximal tumor size reduction of 40% in the FM3A tumor in our study is comparable with the antitumor effect of bleomycin 19) or UFT (a fluorouracil compound) 20) alone. However, in our in vitro study, the concentration equivalent to the achievable maximal plasma concentration (MPC), which is a little higher than 1.0 µg/ml, 21) did not show a cytotoxic effect on Colon 26, Meth-A and FM3A tumor cells, as judged from the IC 50 values of indomethacin in these tumor cells using MTT assay.…”

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confidence: 88%

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Ogino

Higuchi

Murata³

et al. 1999

Japanese Journal of Cancer Research

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The antitumor effect of indomethacin on Colon 26, Meth-A and FM3A tumors was investigated in mice. The prostaglandin E 2 content in tumor tissues was assayed to find out if indomethacin acts on tumors, and the telomerase activity in tumors and somatic tissues (testis, liver, spleen and colon) was also monitored during indomethacin treatment. Growth of Colon 26, Meth-A and FM3A tumors was significantly (P< < < <0.001-0.05) suppressed by indomethacin compared to the untreated controls. The prostaglandin E 2 content in the three tumors was markedly (P< < < <0.001) reduced by indomethacin. Telomerase activity in Colon 26 and FM3A tumors was significantly (P< < < <0.001) lower than that of untreated tumors (80% and 45% decrease versus the controls, respectively), and the activity in Meth-A tumor was slightly decreased (10% decrease versus the control) by indomethacin. Telomerase activity in the somatic tissues was not significantly affected by indomethacin. In summary, this study shows the effectiveness of indomethacin as an antitumor agent against three types of tumors, and suggests that indomethacin affects telomerase activity in tumors in vivo.Key words: Indomethacin -Prostaglandin E 2 -Telomerase activity -Fluorescence-based telomeric repeat amplification protocolThe antitumor effect of indomethacin on tumors in cancer patients 1, 2) and in animals 3, 4) has been described. We previously showed that indomethacin suppresses the growth of Colon 26 tumor in mice by enhancing the cellular immune function and improving cancer cachexia. 5)Indomethacin does not have a cytotoxic effect on Colon 26 tumor cells in vitro, 5) but it may have an antitumor effect via immunological pathways. We previously reported that indomethacin treatment of tumors reduces tumor size less in nude mice (deficient in T-lymphocytes) than in normal mice, compared with untreated tumors. 6)Although these results indicate that the effectiveness of indomethacin as an antitumor agent is, at least in part, due to its modification of T-cell-mediated immune functions, the precise mechanism of tumor growth suppression by indomethacin remains unknown.Recent studies have shown that many proliferating tumor cells retain a certain level of telomerase activity. [7][8][9] We previously reported that tumor growth in Colon 26-bearing mice is significantly suppressed by indomethacin treatment compared with the untreated controls, and that the telomerase activity declines preferentially in tumor tissues, while telomerase activity in somatic tissues is not significantly affected by indomethacin treatment.10) More recently, Kido et al. 11) reported that tumor size reduction by cisplatin treatment correlates with a decline in telomerase activity in tumor tissues.In this study, we transplanted Colon 26, Meth-A and FM3A tumors into normal mice to assess if the effect of indomethacin is independent of tumor cell type. Prostaglandin E 2 synthesis is inhibited by indomethacin, and therefore we measured the prostaglandin E 2 content in tumors to confirm the effect of ind...

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Section: Discussionsupporting

confidence: 88%

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Ogino

Higuchi

Murata³

et al. 1999

Japanese Journal of Cancer Research

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Application of Nuclear Magnetic Resonance for Investigation of the Tumour Microenvironment

Maxwell¹

2000

Blood Perfusion and Microenvironment of Human Tumors

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Indomethacin increases the cytotoxicity of cis-platinum and 5-fluorouracil in the human uterine cervical cancer cell lines SKG-2 and HKUS by increasing the intracellular uptake of the agents

Ogino

Minoura²

2001

Int J Clin Oncol

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Changes of 31P-MR Spectroscopy in Experimental Tumors Following Radiotherapy Compined with 5-Fluorouracil Compound(UFT).

Cited by 4 publications

References 10 publications

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Application of Nuclear Magnetic Resonance for Investigation of the Tumour Microenvironment

Indomethacin increases the cytotoxicity of cis-platinum and 5-fluorouracil in the human uterine cervical cancer cell lines SKG-2 and HKUS by increasing the intracellular uptake of the agents

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Changes of 31P-MR Spectroscopy in Experimental Tumors Following Radiotherapy Compined with 5-Fluorouracil Compound(UFT).

Cited by 4 publications

References 10 publications

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E2 Content and Telomerase Activity in Tumor Tissues

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E2 Content and Telomerase Activity in Tumor Tissues

Application of Nuclear Magnetic Resonance for Investigation of the Tumour Microenvironment

Indomethacin increases the cytotoxicity of cis-platinum and 5-fluorouracil in the human uterine cervical cancer cell lines SKG-2 and HKUS by increasing the intracellular uptake of the agents

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Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues