Using 99mTc-MIBI to Evaluate the Effects of Chemosensitizer on P-glycoprotein in Multidrug-resistant Carcinoma Cells
2005
Objective: To establish a method to
evaluate the effects of chemosensitizer on P-glycoprotein using
99mTc-MIBI, and observe the changes of
99mTc-MIBI uptake kinetics and P-glycoprotein
levels after using verapamil in MDR human breast cells MCF-7/Adr.
Methods: MDR breast carcinoma cells, MCF-7/Adr,
were incubated and different protocols were performed. Protocol I:
a chemosensitizer, verapamil (10 µmol/L), was added into cell
culture medium, while in control group, the same volume of DMEM
was given. Cells were harvested after 2 h incubation with
99mTc-MIBI. Protocol II:
Verapamil (10 µmol/L) was added into cell culture medium and
incubated for 20 min, 40 min, 60 min, 80 min, 8 h, 24 h, 48 h and
72 h respectively. Cells were harvested after 2 h incubation with
99mTc-MIBI. The radioactivity of the cells was
measured and P-glycoprotein expression levels were determined with
immunohistochemical stain. Results: Protocol I:
After 2h incubation with verapamil the cellular uptake of
99mTc-MIBI was remarkably higher than control
group (t=2.33, P<0.05), but there was no difference in
P-glycoprotein expression levels between two groups (P<0.05).
Protocol II: In verapamil group,
99mTc-MIBI uptake was increased with incubation
time prolonging (F=58.2, P<0.05). When verapamil incubation
time surpassed 8 h the 99mTc-MIBI uptake
negatively correlated to the P-glycoprotein expression levels
(r=-0.73, P<0.01). However, when incubation time was less
than 80 min, there was no correlation between
99mTc-MIBI accumulation and P-glycoprotein
levels (r=0.16, P>0.05). Conclusion:
99mTc-MIBI may be used to evaluate the
qualitative as well as quantitative change of P-glycoprotein
expression levels induced by the chemosensitizer, verapamil.
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