Huang Jinxiang,Wang Jijian.Targeting reversal of breast cancer drug resistance by BCRP shRNA expression vector with hTERT promoter in nude mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(06):578-581.
Huang Jinxiang,Wang Jijian.Targeting reversal of breast cancer drug resistance by BCRP shRNA expression vector with hTERT promoter in nude mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(06):578-581.DOI:
Targeting reversal of breast cancer drug resistance by BCRP shRNA expression vector with hTERT promoter in nude mice
Objective To clone human telomerase reverse transcriptase (hTERT) promoter and investigate its specificity to breast cancer cells
and to construct breast cancer resistance protein (BCRP) shRNA expression vector with hTERT promoter
pGenesil-hTERT-shRNA
and observe its influence on doxorubicin resistance of breast cancer cells in experimental animals. Methods Recombinant plasmids pGenesil-CMV-shRNA and pGenesil-hTERT-shRNA were constructed. Fifty nude mice were inoculated with human breast cancer cell line MCF-7/ADR. Forty-five tumor-carrying mice were evenly and randomly divided into a control group
a pGenesil-CMV-shRNA group and a pGenesil-hTERT-shRNA group according to random number tables. Western blotting and RT-PCR were applied to detect BCRP and its mRNA expression in mouse tissues. The tumor volume changes of the tumor-carrying mice were measured. Results The mouse model of human breast cancer was constructed. Western blotting and RT-PCR results showed that
in the pGenesil-CMV-shRNA and pGenesil-hTERT-shRNA groups
the expression levels of BCRP and its mRNA as well as the tumor volumes were significantly reduced as compared with those of the control group (P0.05). The tumor inhibition rate of pGenesil-hTERT-shRNA groups was 68.5%
which were significantly higher than that of the control group (P0.05). Conclusion BCRP shRNA expression vector with hTERT promoter can specifically silence BCRP gene and increase breast cancer cell susceptibility to doxorubicin.