Glivec enhances the down-regulated cytotoxicity of adriamycin in acquired tamoxifen-resistant MCF-7 cell line.
OBJECTIVE
To study the alteration of bax, bcl-2, p170 expressing and the second effect on the adriamycin (ADR) induced cytotoxicity in acquired tamoxifen (TAM)-resistant MCF-7 cell line.


METHODS
The bax, bcl-2, p170 protein expressions were detected by flow cytometry respectively, as well as the content of intracellular ADR. The in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) was performed to evaluate the cytotoxicity of ADR, and also the effect of Glivec on the cytotoxicity of ADR.


RESULTS
The percentages of bax, bcl-2 expressions in the acquired TAM resistant MCF-7 were down-regulated from 53.17+/-1.45% to 28.70+/-1.41% (P <0.01), 41.53+/-2.17% to 37.87+/-1.86% P >0.05 respectively, the p170 was up-regulated from 27.43+/-2.16% to 32.13+/-1.31% (P <0.05), after a 16-week-treatment with 1 x 10(-7) mol/L TAM. Accordingly, the chemosensitivity and the fluorescence intensity of intracellular ADR declined, both of them can be significantly reversed by 10 microg/ml Glivec.


CONCLUSIONS
The acquired TAM resistant MCF-7 accompanied with a declined ADR cytotoxicity, down-regulation of bcl-2/bax-induced apoptosis and up-regulation of p170-induced drug efflux may had a synergic devotion. Glivec may enhance the cytotoxicity of ADR on the acquired TAM-resistant MCF-7 cell line.
Wang
Xiong-wen
XW
Department of Geriatric Medicine, Fourth Affiliated Hospital of Jinan University, Guangzhou 510220, China. awen1029@163.net
Zhang
Ji-ren
JR
Shen
Yan
Y
Zheng
Gang
G
Zhong
Can-can
CC
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011743:Pyrimidines / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; C494826:BAX protein, human; D001549:Benzamides; D006023:Glycoproteins; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D051028:bcl-2-Associated X Protein; D013629:Tamoxifen; D004317:Doxorubicin; D000068877:Imatinib Mesylate