| Abstract |
Aim: To establish a arsenic trioxide (As2O3)-resistant leukemic cell line
to explore the mechanism of resistance to As2O3, and the relationship
between the resistant cell line and the multidrug resistance was also
investigated.
Methods: The arsenic trioxide (As2O3)-resistant leukemic cell line was
established by exposing the cells to the increasing concentration of As2O3.
MTT assay was used to detect the cytotoxicity. Cell cycle was detected by
PI assay. Flow cytometry was used to detect the P-glycoprotein on the
surface of the cells, the intracellular concentration of DNR, and the
immune type of the cells.
Results: The cell doublings time and the cell cycle of the arsenic
trioxide (As2O3)-resistant leukemic cell line, K562/AS2, is similar to
that of K562. The relative resistant fold of K562/AS2 to As2O3, DNR, VP16
and Ara-C was 7.4, 2.9, 3.8 and 1.1, respectively. The relative resistant
fold of multidrug resistant cell line, K562/AS2, to As2O3, DNR, VP16 and
Ara-C was 0.8, 9.4, 2.5 and 0.9, respectively. The fluorescence of the
P-glycoprotein on the surface or of the DNR inside the cells detected was
not significantly different between the K562 and the K562/AS2 cell lines.
Conclusions: A cell line, K562/AS2, resistant to clinical achieving level
(2 mumol/L) of As2O3 has been established. The relative resistant fold of
K562/ AS2 to As2O3 is about 7.4 fold to the parent K562 line sensitive to
As2O3. Partial resistance of K562/AS2 to DNR and VP16 is observed , the
mechanism of which is unrelated to the P-gp, the expression product of
multidrug resistance gene 1 (mdr1).
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