In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug.
In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug.
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体内和体外评估Combretastatin A-4及其磷酸钠前药。
DOI：
10.1038/sj.bjc.6692174
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发表时间：
1999-12
影响因子：
8.8
通讯作者：
Bibby, MC
中科院分区：
文献类型：
--
作者：
Grosios, K;Holwell, SE;McGown, AT;Pettit, GR;Bibby, MC
在皮下和原位移植的实验性结肠肿瘤模型中检查了考布他汀A-4及其前药考布他汀A-4磷酸二钠的抗肿瘤作用和作用机制。此外，还在HUVEC培养物中检查了这些化合物直接干扰内皮细胞行为的能力。Combretastatin A-4（150 mg kg-1，腹膜内（i. p.））及其水溶性前药（100 mg kg-1，i. p.）在MAC 15 A皮下（s.c.）结肠肿瘤在用前药处理的MAC 15原位肿瘤和SW 620人结肠肿瘤异种移植物中获得了类似的血管效应。更重要的是，在原位模型中，在血管化转移性沉积物中观察到坏死，但在无血管的继发性沉积物中未观察到坏死。在HUVEC细胞中检查引起这些作用的可能机制。在此，细胞网络在I型小牛皮肤胶原蛋白层中形成，并且当与非细胞毒性浓度的考布他汀A-4或其前药孵育时，这些网络被完全破坏。这种作用在4小时开始，到24小时完成。相同的非细胞毒性浓度导致处理后1 h F-肌动蛋白和β-微管蛋白的解体。总之，考布他汀A-4及其前药在MAC 15 A s.c.中引起广泛坏死。和原位结肠癌和转移，导致抗肿瘤作用。在无血管肿瘤结节中未观察到坏死，提示血管作用机制。© 1999癌症研究运动
The anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg–1, intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg–1, i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and β-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action. © 1999 Cancer Research Campaign
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DOI：
10.1083/jcb.97.5.1648
发表时间：
1983-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Montesano R;Orci L;Vassalli P
通讯作者：
Vassalli P
影响因子：
8.8
作者：
Ching LM;Joseph WR;Baguley BC
通讯作者：
Baguley BC
DOI：
10.1002/path.1700440220
发表时间：
1937-11-01
期刊：
JOURNAL OF PATHOLOGY AND BACTERIOLOGY
影响因子：
--
作者：
Clearkin, PA
通讯作者：
Clearkin, PA
影响因子：
3.1
作者：
COWEN, SE;BIBBY, MC;DOUBLE, JA
通讯作者：
DOUBLE, JA
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR