The Anti-metastasis Mechanisms Of Taxol And Camptothecin And Analogues

Taxol, Camptothecin (CPT) and its analogues have been widely used as first-line anticancer drugs, especially for breast, ovary, lung, colon cancers or melanoms. In recent years the two drugs have been found to exhibit anti-metastasis effect. This article reports anti-metastasis mechanisms of taxol, CPT and its analogues.Part I Metastasis inhibition of Taxol, CPT and its analogues1. Anti-adhesion, anti-invasion, inhibitory effect of metalloproteinase secretion of Taxol and CPTThe results showed that inhibition rate of 0.1nM,10 nM Taxol on B16F10 adhesion to FN were 28 %和 42 % (P<0.05) , the inhibition rate of B16F10 adhesion to LN were 32%和 39% (P<0.05) . 0.1 nM CPT had no significant effect on B16F10 to FN, but the inhibition effect of 10nM CPT to FN and LN were 37 % and 13%) respectively. The results showed that both Taxol and CPT had the anti-adhesion effect of B16F10 to FN and LN, at the same concentrations Taxol showed higher inhibitory effect than CPT.By testing the anti-migration effect of Taxol and CPT on B16F10 cells, the percentage of migration cells in the control group were 48 + 0.17 %, after treatment with 0.01μM Taxol or CPT for 12 h, the percentage of migration cells were reduced to 22±0.17 % and 29±0.16 % (p<0.05). The migration velocities in the control group were 0.29 ±0.05 μm/min, while after treatment with 10nM Taxol or CPT for 12 h, the migration velocities were reduced to 0.24±0.02 μm/min,0.25±0.03 μm/min (p<0.05). The results showed both Taxol and CPT had anti-migration effect of B16F10 cells.The gelatin zymography of metalloproteinase secretion of HT1080 cells demonstrated that after 0.0lμM, 1μM Taxol treatment for 24 h, the inhibition rate of MMP9 secrection were 75.1 % and 97.6 %, inhibition rate of MMP2 secretion were 9.4 % and 94.0 % . Besides, after 0.01 μM, 1μM CPT treatment for 24 h, the inhibition effect of MMP9 secrection were 73.9 % and 89.7 %, inhibition effect of MMP2 secretion were 14.7 % and 94.0 %. The results showed that Taxol and CPT could inhibit the MMP2 and MMP9 secretion of HT1080 cells.In the transwell chamber experiment, the anti-invasive effect of 0.001μM, 0.01μM and 0.1μM Taxol on B16BL6 cells were 25%, 55% and 77 % seperately, it showed that Taxol conld inhibit the B16BL6 invasion significantly. But 0.00lμM, 0.01μM and 0.1μM CPT had no anti-invasive effect on B16BL6 cells.2. The anti-angiogenesis effect of Taxol, CPT and its analoguesMTT method showed that Taxol, TPT, 10-HCPT had a strong anti-proliferation effect on...