LEUKOCYTE-INDUCED ANGIOGENESIS AND SUBCUTANEOUS GROWTH OF B16 MELANOMA
LEUKOCYTE-INDUCED ANGIOGENESIS AND SUBCUTANEOUS GROWTH OF B16 MELANOMA
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DOI：
10.1089/cbr.1994.9.163
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发表时间：
1994-06-01
期刊：
影响因子：
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通讯作者：
FIDLER, IJ
中科院分区：
文献类型：
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作者：
GUTMAN, M;SINGH, RK;FIDLER, IJ
我们研究了全身给予阿霉素 (DXR) 导致同基因小鼠皮下组织 B16 黑色素瘤生长迟缓的机制。将 DXR 或盐水静脉注射 (i.v.) 至 C57BL/6 小鼠中，并在 DXR 治疗后第 3、7 或 21 天皮下 (s.c.) 植入 B16-BL6 细胞。在 DXR 预处理的小鼠中，肿瘤生长速度比对照（盐水处理）小鼠要慢。使用对 DXR 具有抗性的 B16 变体重复实验，得到了相似的结果。肿瘤生长迟缓与通过计数骨髓细胞、循环白细胞和腹膜巨噬细胞监测的骨髓抑制程度相关。在用 1 x 10(7) 活同基因脾细胞重建的 DXR 预处理小鼠中，sc。肿瘤生长速度与对照小鼠相似。在 BALB/c 无胸腺裸鼠中重复 DXR 治疗和脾细胞重建实验。结果非常相似。 s.c.的成长肿瘤的发生与瘤周血管分布程度直接相关。这些数据表明，除了其有据可查的直接抗肿瘤作用外，DXR 还可以通过产生骨髓抑制来延缓肿瘤生长，从而抑制宿主细胞诱导的肿瘤血管生成。
We investigated the mechanism(s) by which systemic administration of doxorubicin (DXR) produced growth retardation of B16 melanomas in the subcutis of syngeneic mice. DXR or saline was injected intravenously (i.v.) into C57BL/6 mice, and B16-BL6 cells were implanted subcutaneously (s.c.) on day 3, 7, or 21 after DXR treatment. In the DXR-pretreated mice, the tumors grew at a slower rate than in control (saline-treated) mice. The experiments were repeated with a B16 variant resistant to DXR with similar results. Tumor growth retardation correlated with extent of myelosuppression monitored by counting bone marrow cells, circulating leukocytes and peritoneal macrophages. In DXR-pretreated mice reconstituted with 1 x 10(7) viable syngeneic spleen cells, the sc. tumors grew at a rate similar to that in control mice.DXR treatment and spleen cell reconstitution experiments were repeated in BALB/c athymic nude mice. The results were very similar. The growth of s.c. tumors was directly correlated with the degree of peritumoral vascularity. These data indicate that in addition to its well-documented direct antitumor effects, DXR may produce retardation of tumor growth by producing myelosuppression and, hence, inhibition of host cell-induced tumor angiogenesis.