| PAN Yao-zhen,SUN Cheng-yi,WANG Yu-zhi.Reversal of multidrug resistance with mdr1 antisense oligodeoxynucletides promoted by ionizing radiation[J].Chinese Journal of Radiological Medicine and Protection,2005,25(4):342-345 |
| Reversal of multidrug resistance with mdr1 antisense oligodeoxynucletides promoted by ionizing radiation |
| Received:December 30, 2004 |
| DOI： |
| KeyWords:Ionizing radiation Multidrug resistance Antisense oligodeoxynucletides Gene transfection Nude mice |
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| Abstract:: |
| Objective To investigate the reversal of multidrug resistance (MDR) by MDR gene mdr1 antisense oligodeoxynucletides(ASON) in combination with radiation in KBv200 cell line. Methods Comparison of 50% inhibitory concentration (IC50) of vincristine-resistant KBv200 cell line was carried out with the MTT method.One group of cells of that cell line were transfected by lipo-ASON in combination with ionizing radiation and another group of cells were thansfected without such combination. The expression of mdr1 at mRNA level was examined by RT-PCR. Flow cytometry was used to demostrated the positive rate of the mdr1 gene product P-glucoprotein(P-gp) in lipo-ASON-treated cells with two different methods. Nude mice were transplanted with the resistant KBv200 cell line.Afterwards mdr1 ASON was injected into the tumor 1 hour after local 2 Gy 60Coγ-irradiation.The tumor-suppressing rate and tumor-suppressing curve were observed in these two groups of cells after treatment with vincristine(VCR). Results The inhibitory efficiency of lipo-ASON plus ionizing radiation was higher than that without ionizing radiation(P<0.05). The IC50, the mdr1 mRNA expression level,and P-gp-positive rate of irradiated KBv200 cells were all significantly lower than those of unirradiated cells(P<0.05). The results showed that the differences of tumor growth curves were significant between irradiated and unirradiated cell groups(P<0.01) as well as the control group (P<0.01). Conclusion The reversal effect of mdr1 ASON plus ionizing radiation is stronger on resistant cell line than that of mdr1 ASON alone. |
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