Analysis of the antitumoral mechanisms of lipopolysaccharide against glioblastoma multiforme.
Our objective was to analyze the lipopolysaccharide (LPS) antitumoral effect upon glioblastoma, including whether the lipid A subunit alone can elicit glioblastoma regression, whether dexamethasone suppresses this response to LPS, whether B and T lymphocytes factor in this response, and whether this antitumoral effect of LPS provides resistance against subsequent challenge with glioblastoma. Mice (BALB/c, nude or SCID) implanted with s.c. DBT glioblastomas were treated with LPS (with or without dexamethasone) or with lipid A. A subset of BALB/c mice in which s.c. DBT glioblastomas had previously been eradicated using LPS were re-implanted with s.c. or intracranial (i.c.) DBT cells. For mice with s.c. tumors, mean tumor masses (MTM) were compared between groups. Survival was compared for mice with i.c. tumors. Lipid A caused near complete tumor regression of DBT glioblastomas in BALB/c mice (p<0.0001). Dexamethasone did not alter the antitumoral effect of LPS (p=0.48). LPS reduced the MTM of s.c. glioblastomas in T lymphocyte-deficient nude mice, but not as effectively as in immunocompetent mice. The antitumoral response to LPS for T and B lymphocyte-deficient SCID mice bearing DBT glioblastomas was similar to that for nude mice. Eradication of s.c. DBT glioblastoma in BALB/c provided partial resistance to subsequent challenge with s.c. or i.c. glioblastoma. We conclude that the LPS-mediated antitumoral response against glioblastoma is dependent upon the lipid A subunit of LPS, partially dependent upon T lymphocytes, independent of B lymphocytes, unaffected by dexamethasone and provides partial protection against subsequent challenges with glioblastoma.
Won
Eun Kyung
EK
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Zahner
Michael C
MC
Grant
Elizabeth A
EA
Gore
Pankaj
P
Chicoine
Michael R
MR
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D008050:Lipid A / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D013045:Species Specificity
D018931:Antineoplastic Agents, Hormonal; D008050:Lipid A; D008070:Lipopolysaccharides; D003907:Dexamethasone