Taxol inhibits melanoma metastases through apoptosis induction, angiogenesis inhibition, and restoration of E-cadherin and nm23 expression.
An in vivo melanoma spontaneous metastases model was adopted to study the molecular mechanisms of the anti-metastatic effect of Taxol. The morphology of melanoma cells in the melanoma tissue lesions was examined by hematoxylin/eosin (H&E) staining and electron microscopy. The in situ programmed cell death was tested by TUNEL analysis. Vascular endothelial growth factor (VEGF) and E-cadherin expression were detected by immunohistochemistry. The metastases suppressor gene nm23 mRNA expression level was analyzed by in situ hybridization. The results showed that i.p. injection of Taxol at 5 mg/kg per day for three weeks significantly inhibited metastases formation in the pulmonary of mice. Taxol induced melanogenesis and apoptosis in the melanoma cells, inhibited angiogenesis in melanoma tissue lesions, and reduced the expression of VEGF. Conversely, Taxol increased the expression of E-cadherin and nm23. In conclusion, administration of Taxol in the early stage of melanoma metastases can significantly inhibit melanoma metastases. This effect was possibly related to apoptosis induction, tumor angiogenesis inhibition, and restoration of the metastasis suppression ability.
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. wangfangpumc@hotmail.com
Fang
F
Wang
Yu
Y
Cao
WanZhou
W
Zhao
Hongyan
H
Liu
Zhaodi
Z
Fu
Rui
R
Han
D020533:Angiogenesis Inhibitors; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000096:biosynthesis*; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005456:Fluorescent Dyes; D006416:Hematoxylin; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D054778:NM23 Nucleoside Diphosphate Kinases; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D009701:Nucleoside-Diphosphate Kinase; D017239:Paclitaxel / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D004396:Coloring Agents; D005456:Fluorescent Dyes; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D017239:Paclitaxel; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin