| Paclitaxel(Taxol) is one kind of broad-spectrum anti-tumor drugs, which has an effect on microtubule. It has been shown to be widely used in the treatment of patients with advanced malignant solid tumors such as ovary cancer, breast cancer and lung cancer, but there has been no report about its application in clinical treatment of leukemia in china. Although it was reported that taxol could inhibit the proliferation of many leukemia cell lines including K562, HL-60 and so on in vitro, the result of a phase I clinical study on the application of taxol alone at abroad was unsatisfactory. No report has covered the effects of the combination of taxol with some common chemotherapeutic drugs, such as adriamycin (ADM), cytosine arabinoside (Ara-C) on proliferation of human leukemia cells. The present study aims to observe the anti-proliferation effects of the combination of taxol with ADM, Ara-C and each agent alone on leukemia cell lines K562 and HL-60 in vitro, which may providesome clues to clinical application.Materials and MethodsThe human acute erythroleukemia cell line K562 and human acute granulocytic leukemia cell line HL-60 were provided by the Cancer Institute of College of Medicine of ZheJiang University. Taxol was provided by Sichuan Taiji Pharmaceutical Co Ltd, ADM was provided by Zhejiang Haizheng Pharmaceutical Co Ltd, Ara-C was provided by Shanghai Hualian Pharmaceutical Co Ltd. This study was divided into two parts. One was single agent experiment, and the other was agents combination experiment. There were four groups for single agent experiment: taxol group with the concentration of 0.125-4μ g/mL, ADM group with the concentration of 0.3125-10 μ g/mL, Ara-C group with the concentration of 2-64 μ g/mL and negative control group. There were also four groups for agents combination: taxol+ADM group, taxol+Ara-C group, taxol+ADM+Ara-C group and negative control group. According to the results from single agent experiment, we chose 0.3 μ g/mL ADM and 2 μ g/mL Ara-C in which concentration their inhibition rates on K562 or HL-60 were about 10-30%, and different concentrations of taxol. After the cells had been cultured for 24, 48 and 72 hours, we detected the anti-proliferation effects of the agents on the cell lines in all groups by method of MTT, then calculated the inhibition rate, figured out the 50% inhibition concentration (IC50) value. The statistic precession was carried out in SPSS 10.0 for windows. IC50 value was figured out by linear regression. Comparison with inhibition rates between two groups was performed by Mest and the P value less than 0.05 was considered statistically significant.ResultsSingle agent experiment showed that taxol, ADM and Ara-C had various degrees of inhibitory effects on the cell lines K562, HL-60 and their inhibition rates had obvious concentration-effect and time-effect relationship. The IC50 values of taxol, ADM and Ara-C on K562 after 72h were 0.11 μ g/mL, 0.18 μ g/mL and 3.71 μ g/mL respectively, and those on HL-60 were 0.37 μ g/mL, 0.22 μ g/mL and 1.93 μ g/mL respectively. From the above data, the inhibitory effect of taxol on K562 is much stronger than that on HL-60.Agents combination experiment showed that compared with taxol alone, combination of taxol with ADM or Ara-C or both of them has a remarkable increase in anti-proliferation activity on cell lines K562 and HL-60 (P<0.05) . Although the highest inhibitory effect was observed in the combination of three agents, but there was no significant difference between taxol with ADM and three agents (P>0.05), and the difference between taxol with Ara-C and three agents was significant (P<0.05). It suggested that the effect of the combination of three agents was similar to that of taxol with ADM. When 0.3 μ g/mL ADM was combined with 0.125 μ g/mL taxol, the inhibition rate rose from 25.31% to 55.49% and this effect was equal to that of double-concentration of ADM alone. When the concentration of taxol rose to 0.5 u g/mL, its inhibitory effect with ADM was equal to that of eigh... |
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