Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy.
Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy.
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DOI：
10.1111/j.1349-7006.1999.tb00724.x
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发表时间：
1999-12
期刊：
影响因子：
--
通讯作者：
Sato Y
中科院分区：
文献类型：
--
作者：
Nihei Y;Suzuki M;Okano A;Tsuji T;Akiyama Y;Tsuruo T;Saito S;Hori K;Sato Y
微管蛋白结合剂(TbA)可减少实体瘤的肿瘤血流，抑制实体瘤细胞的有丝分裂，但目前尚不清楚哪些作用参与了实体瘤的生长抑制。我们评价了几种TBAs，如磷酸抗癌素A-4(CS A-4)、AC-7700、新型CS A-4衍生物、秋水仙碱、E7010和长春花碱，对皮下组织的抗血管和抗有丝分裂作用。小鼠结肠腺癌(C26)。可耐受剂量的长春花碱和E7010强烈抑制肿瘤生长，并诱导肿瘤细胞有丝分裂停止，而不影响肿瘤的血流灌注。秋水仙碱对肿瘤生长和灌注无影响。然而，当注射剂量增加到致死范围时，这些药物显著减少了肿瘤的灌注量，并导致肿瘤组织的坏死。在可耐受剂量范围内，AC-7700强烈抑制肿瘤生长，减少肿瘤血流灌注，CS A-4磷酸也表现出中等的抗血管作用。为了评估TBAs的抗血管活性在肿瘤生长抑制中的作用，排除其对肿瘤细胞的直接细胞毒作用，我们在体外建立了对TBAs具有耐药性的c26/ACR。虽然E7010对S.C.的抑制作用减弱。C26/ACR肿瘤生长与其对野生型C26的影响相比，AC-7700对这两种细胞株都具有较强的抑制作用。这些结果表明，TBAs对实体瘤具有抗血管和抗有丝分裂作用，不同药剂的有效剂量范围有显著差异，且其抗血管作用不依赖于对肿瘤细胞的直接细胞毒作用。
Tubulin binding agents (TBAs) reduce tumor perfusion and inhibit mitosis of tumor cells in solid tumors, but it is not clear which effects contribute to the suppression of solid tumor growth. We evaluated the antivascular and antimitotic effects of several TBAs, combretastatin A‐4 (CS A‐4) phosphate, AC‐7700, a novel CS A‐4 derivative, colchicine, E7010, and vinblastine, on subcutaneous (s.c.) murine colon26 adenocarcinoma (c26). Tolerable doses of vinblastine and E7010 strongly inhibited tumor growth and induced mitotic arrest of tumor cells without affecting tumor perfusion. Colchicine had no effect on tumor growth and perfusion. When the injected dose was increased to the lethal range, however, these drugs markedly reduced tumor perfusion and caused necrosis of tumor tissue. Within the tolerable dose range, AC‐7700 both strongly suppressed tumor growth and reduced tumor perfusion, and CS A‐4 phosphate also exhibited a moderate antivascular effect. To evaluate the contribution of antivascular activity of TBAs to tumor growth suppression, excluding their direct cytotoxic effect on tumor cells, we established c26/acr, which is resistant to TBAs in vitro. Although E7010 showed a reduced suppressive effect on s.c. c26/acr tumor growth as compared with its effect on wild‐type c26, AC‐7700 remained potent against both cell lines. These results indicate that TBAs exert antivascular and antimitotic effects on solid tumors with marked differently effective dose ranges from agent to agent, and that the antivascular effect of TBAs inhibits solid tumor growth independently of the direct cytotoxic effect on tumor cells.
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影响因子：
7.3
作者：
CUSHMAN, M;NAGARATHNAM, D;HAMEL, E
通讯作者：
HAMEL, E
DOI：
10.1111/j.1349-7006.1999.tb00850.x
发表时间：
1999-09-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Nihei, Y;Suga, Y;Tsuruo, T
通讯作者：
Tsuruo, T
影响因子：
7.3
作者：
ANDRADE, SP;HART, IR;PIPER, PJ
通讯作者：
PIPER, PJ
影响因子：
8.4
作者：
BAGULEY, BC;HOLDAWAY, KM;ZWI, LJ
通讯作者：
ZWI, LJ
影响因子：
7.3
作者：
Ohsumi, K;Nakagawa, R;Tsuji, T
通讯作者：
Tsuji, T