Cyclooxygenase-2 Inhibitor Induces Apoptosis and Enhances Cytotoxicity of Various Anticancer Agents in Non-Small Cell Lung Cancer Cell Lines
2000
In
recent years, a combination of two demographic phenomena, an increase
in the number of older people in the population and an increase in the
incidence of lung cancer with age, has made it mandatory to develop
therapeutic modalities with less toxicity for the treatment of
inoperable elderly patients with lung cancer. Our study shows that a
cyclooxygenase (COX)-2 inhibitor, nimesulide, can inhibit proliferation
of non-small cell lung cancer cell lines in vitro in a
dose-dependent manner, in part by inducing apoptosis even at clinically
achievable low concentrations. Our observations also suggest that the
responsiveness of non-small cell lung cancer to COX-2 inhibitors does
not require the presence of wild-type p53, but may be influenced by the
degree of COX-2 expression. In addition, we found that nimesulide, when
used in combination at clinically achievable concentrations, reduced
the IC 50 values of various anticancer agents by up to 77%,
although the level of reduction varied considerably. Because our
previous studies have indicated a significantly increased COX-2
expression in up to 70% of adenocarcinoma cases, the present findings
are of great clinical interest. In conjunction with the recent
development of next generation, highly selective COX-2 inhibitors, they
can be expected to lead to even greater efficacy of their use as
adjuncts to various anticancer agents for the treatment of high-risk
patients without compromising their quality of life.
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