Won Eun Kyung, Zahner Michael C, Grant Elizabeth A, Gore Pankaj, Chicoine Michael R
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Anticancer Drugs. 2003 Jul;14(6):457-66. doi: 10.1097/00001813-200307000-00012.
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.
我们的目标是分析脂多糖（LPS）对胶质母细胞瘤的抗肿瘤作用，包括仅脂质A亚基是否能引发胶质母细胞瘤消退、地塞米松是否会抑制对LPS的这种反应、B和T淋巴细胞在该反应中是否起作用，以及LPS的这种抗肿瘤作用是否能提供对随后胶质母细胞瘤攻击的抗性。将皮下植入DBT胶质母细胞瘤的小鼠（BALB/c、裸鼠或SCID小鼠）用LPS（加或不加地塞米松）或脂质A进行治疗。一部分先前使用LPS根除了皮下DBT胶质母细胞瘤的BALB/c小鼠再次皮下或颅内植入DBT细胞。对于患有皮下肿瘤的小鼠，比较各实验组间的平均肿瘤质量（MTM）。比较患有颅内肿瘤小鼠的生存率。脂质A导致BALB/c小鼠的DBT胶质母细胞瘤几乎完全消退（p<0.0001）。地塞米松未改变LPS的抗肿瘤作用（p=0.48）。LPS降低了T淋巴细胞缺陷的裸鼠皮下胶质母细胞瘤的MTM，但效果不如免疫活性小鼠。携带DBT胶质母细胞瘤的T和B淋巴细胞缺陷的SCID小鼠对LPS的抗肿瘤反应与裸鼠相似。在BALB/c小鼠中根除皮下DBT胶质母细胞瘤可对随后皮下或颅内胶质母细胞瘤攻击提供部分抗性。我们得出结论，LPS介导的针对胶质母细胞瘤的抗肿瘤反应依赖于LPS的脂质A亚基，部分依赖于T淋巴细胞，不依赖于B淋巴细胞，不受地塞米松影响，并能对随后的胶质母细胞瘤攻击提供部分保护。
