Indomethacin Enhances the Cytotoxicity of VCR and ADR in Human Pulmonary Adenocarcinoma Cells
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SHUNSUKE KOBAYASHI, SHINICHIRO
OKADA, HIROYUKI YOSHIDA and
SHIGEFUMI FUJIMURA
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Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980
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The ability of anti-inflammatory agents to modulate cellular sensitivity to anticancer drugs was investigated for
pulmonary carcinoma cells in vitro. We examined the drug sensitivity of two pulmonary adenocarcinoma cell
lines (76-2, 77-4) in the presence of two drugs, an anticancer drug and an anti-inflammatory agent, for 72 hr by
the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay with 96 well plates.
Anticancer drugs used for screening test were cyclophosphamide ( CPM), mitomycin C (MMC), adriamycin
(ADR), 5-fluorouracil (5FU), vindesine (VDS), cisplatin (CDDP), cytarabine (Ara C), methotrexate (MTX),
etoposide (VP-16), and vincristine (VCR). Anti-inflammatory agents examined as modulators to anticancer
drugs were aspirin, mefenamic acid, ibuprofen, sulindac, piroxicam, phenacetin, dicrofenac, ketoprofen,
tolmetin and indomethacin. Screening tests showed indomethacin to be the most effective modulator, resulting
in more than a 3-fold increase in cytotoxicity of VCR as compared with that produced by VCR alone. Study of
each of the ten anticancer drugs in combination with indomethacin showed VCR to be the most effective
anticancer drug in this combination. In 76-2 cells, the concentration of VCR producing 50% growth inhibition
(IC50) for VCR alone and VCR in combination with 2 micro g/ml indomethacin were 1.58+/-0.16
and 0.52+/-0.1 ng/ml respectively, which represents a 3-fold decrease. In 77-4 cells, the IC50 for
VCR alone and VCR in combination with 2 micro g/ml indomethacin were 2.86+/-0.2 and 0.52+/-0.11 ng/ml
respectively, which represents a 3.8-fold decrease. Our studies indicate that clinically achievable concentrations
of indomethacin may be useful in modulating VCR resistance in human pulmonary adenocarcinoma cells, so
that combined use of VCR and indomethacin may be of potential clinical significance in the treatment of lung
cancer.
Key words---
biochemical modulator; indomethacin; VCR; lung cancer; cell line
Tohoku J. Exp. Med., 1997, 181, 361-370
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