Antitumor effect of inhalatory lipopolysaccharide and synergetic effect in combination with cyclophosphamide.
BACKGROUND
Macrophage cells differentiate into killer macrophages, named M1 macrophages, that effectively eliminate cancer cells by generating cytokines. We examined the feasibility of a lung cancer therapy using lipopolysaccharide (LPS), which triggers this differentiation. It is expected that the delivery via inhalation of LPS directly into the lungs, where alveolar macrophages reside abundantly, would be effective at minimizing the possible toxic effect of LPS.


METHODS
We determined the effects of intratracheal insufflation of LPS on (i) the exudation of lactate dehydrogenase, (ii) generation of tumor necrosis factor-α and interleukin-12, and (iii) tumor metastases in Lewis lung carcinoma-bearing C57BL/6 mice.


RESULTS
Pulmonary insufflation of LPS resulted in a consistent accumulation of tumor necrosis factor-α, and transient increase in interleukin-12 without significant release of lactate dehydrogenase from the lung cells. In addition, a significant antitumor effect of LPS was observed; and this antitumor effect was potentiated by combination of LPS with the antitumor agent cyclophosphamide.


CONCLUSIONS
Pulmonary inhalation of LPS combined with a chemotherapeutic agent is a promising approach to lung cancer therapy.
Hirota
Keiji
K
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki Noda, Chiba 278-8510, Japan.
Oishi
Yusuke
Y
Taniguchi
Hiroaki
H
Sawachi
Keiichi
K
Inagawa
Hiroyuki
H
Kohchi
Chie
C
Soma
Gen-Ichiro
G
Terada
Hiroshi
H
D000280:Administration, Inhalation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D003520:Cyclophosphamide