| Title | [The relationship between multi-drug resistance and proportion of leukemia stem cells and expression of drug transporters in drug-resistant leukemia K562/ADM cells] | | Author(s) | Yi J, Chen J, Sun J, Wei HL | | Institution | Laboratory Center for Medical Science, School of Medicine, Lanzhou University, Lanzhou, China. | | Source | Zhonghua Yi Xue Za Zhi 2009 Jul 7; 89(25):1741-4. | | Abstract | OBJECTIVE: To investigate the drug resistance, proportion of leukemia stem cells (LSC) and expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cell population.
METHODS: The multidrug-resistant leukemia K562/ADM cell and its parental K562 cell were used as the model cells. The drug sensitivity was tested with a MTT assay. Flow cytometry was employed to detect the immunophenotype of stem cells and the expression of P-gp and BCRP. The self-renewal and proliferating potential were examined with methylcellulose colony-forming unit assay.
RESULTS: K562/ADM cells were highly resistant to adriamycin, daunorubincin and etoposide. The amount of CD34+, CD123+ and CD34+ CD38- cells in K562/ADM cells was much higher than that in K562 cells, and the proportion of CD34+ CD38- CD123+ cells (LSC) in K562/ADM cells was (5.23 +/- 0.21)% versus (1.27 + 0.17)% in K562 cells, which was 4.12-fold higher than that in K562 cells. Both P-gp and BCRP were overexpressed in K562/ADM cells relative to K562 cells, and the K562/ADM cells coexpressing P-gp and BCRP were 11.25-fold higher over K562 cells. The proportion of CD34+ CD38- CD123+ BCRP+ and CD34+ CD38- P-gp+ BCRP+ cells in K562/ADM cells were (4.13 +/- 0.40)% and (5.80 +/- 1.19)% respectively, which were 3.66- and 11.37-fold higher than the same cells in K562 cells [(1.13 +/- 0.15)% and (0.51 +/- 0.01)%]. Furthermore, drug-resistant K562/ADM cells displayed 4.17-time greater colony-forming ability over the parent K562 cells, corresponding to the proportion of LSCs in K562/ADM cells.
CONCLUSIONS: The ABC transporters-overexpressing LSC population exists in drug-resistant leukemic K562/ADM cells relative to drug-sensitive K562 cells, and the drug-resistant LSCs may be the source of chemotherapeutic resistance of leukemia. | | Language | chi | | Pub Type(s) | English Abstract
Journal Article
| | PubMed ID | 19862976 |
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