[Erythropoietin increases transferrin receptor expression and the impact of erythropoietin on K562 leukemic cell cycle].
OBJECTIVE
Functionally, erythropoietin (EPO) can promote the proliferation and growth of erythroid progenitor cells, and it is widely used in the treatment of anemia in chronic diseases caused by tumor and inflammation. However, it is unclear whether EPO has any effect on tumor cell iron metabolism and tumor cell proliferation. The purpose of this study was to explore the effects of recombinant human EPO (rhEPO) on the expression of transferrin receptor (TfR, CD(71) antigen) of leukemic cell K562 and its relation to cell cycle.


METHODS
In vitro culture of K562 cell was performed with additions of various concentrations of rhEPO and Fe. Treatments were terminated at 24 h and 72 h, respectively. Then each group of cells was incubated with FITC-IgG antibody to CD(71) or PI, a kind of DNA dye. And TfR expression and DNA synthesis status were analyzed by flow-cytometry.


RESULTS
(1) The expression of TfR by K562 cells increased significantly when incubated for 72 h with different concentrations of rhEPO. The measurement values of 5 U/ml, 10 U/ml and 20 U/ml groups were 12.2 +/- 1.40, 10.7 +/- 0.99 and 11.1 +/- 0.90, respectively. They were markedly increased when compared with that of control group (6.27 +/- 0.11, P < 0.05). (2) When incubated with rhEPO (5 u/ml) alone or combined with FeCl(3) (100 micro mol/L), the percentages of cells in S phase were 51.1% and 59.6%, respectively. They significantly increased when compared with that of control group (42.9%, P < 0.05).


CONCLUSIONS
Iron is very important for the proliferation of both normal cells and leukemic cells. It is essential to the activity of ribonucleotide reductase (RR). The authors hypothesized that rhEPO would increase the expression of TfR and intracellular iron content of leukemic cells, which would enhance the DNA synthesis and cell proliferation. Therefore, the clinical application of rhEPO to promote erythropoiesis of cancer patients should be cautious.
Zhou
Mi
M
Department of Pediatrics, The Second Huaxi Hospital, Sichuan University, Chengdu 610041, China.
Liao
Qing-kui
QK
Li
Feng-yi
FY
Gao
Ju
J
Fu
Ren-yi
RY
Luo
Chun-hua
CH
Li
Qiang
Q
Jia
Cang-song
CS
D002453:Cell Cycle / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D011990:Receptors, Transferrin / Q000378:metabolism*; D011994:Recombinant Proteins
D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D004921:Erythropoietin