14員環マクロライド系抗菌薬の非小細胞肺癌に対する tumor dormancy therapy に関する基礎的・臨床的検討

Abstract

Clarithromycin (CAM), a 14-membered macrolide, has some effects as a biological response modifier in addition to its antibiotic effects. Long-term CAM treatment has been shown to improve the prognosis of patients with unresectable non-small cell lung cancer, including their quality of life. In the present study, I examined the suppression of Lewis lung carcinoma (LLC) cell proliferation, expression of mRNAs for integrin and TGF -β in LLC cells, suppression of lung metastasis and cytokine mRNA in spleen cells of mice lung cancer model by CAM. Proliferation of LLC cells and the expression of mRNAs for integrin (α4, α6, β1) and TGF-β were suppressed by CAM, CAM decreased the number of lung metastasis nodules in LLC-bearing mice. The expression of mRNAs for IL-12 and IFN-γ in spleen cells was increased after CAM treatment. On the contrary, the expression of mRNAs for IL-6 and IL-10 was decreased. Furthermore I determined the in-vivo effect of CAM on metastasis in unresectable non -small cell lung cancer patients, and cytokine mRNA expression in peripheral blood mononuclear cells from patients. Incidence of lung cancer metastasis was lower in CAM- treated patients than in untreated ones. The expression of both IL-12 and IFN-γ mRNAs was increased by CAM, while the expression of both IL-6 and IL-10 mRNAs was decreased. These results suggest that CAM exhibits directly and indirectly antineoplastic activity and that CAM treatment is cosidered a promising candidate for tumor dormancy therapy.