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Ai Zheng. 2005 Aug;24(8):924-9.

[Correlation of HERG K+ channel protein expression to chemosensitivity of tumor cells to doxorubicin and its modulation by erythromycin].

[Article in Chinese]

Author information

1
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.

Abstract

BACKGROUND & OBJECTIVE:

Previous studies have found that HERG, a kind of K(+) channel protein, is expressed in some cancers, but its expression is weak or lost in normal tissues. This study was to investigate HERG expression in various cancer cell lines, its correlation with chemosensitivity of cancer cells to doxorubicin, and its biochemical modulation.

METHODS:

HERG expression in human colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human lung carcinoma cell line A549, and human high-metastatic giant cell lung carcinoma cell line PG was analyzed by Western blot. After transfection of herg gene, the cytotoxicity of doxorubicin, erythromycin (a HERG K+ channel blocker), or doxorubicin in combination with erythromycin to cancer cells was analyzed by MTT assay. Intracellular content of doxorubicin was observed under fluorescent microscope.

RESULTS:

HERG protein level was higher in HT-29, MCF-7, and PG cells than in A549 cells. A549 cells were more sensitive to doxorubicin than HT-29 cells. The 50% inhibitory concentration (IC(50)) of doxorubicin was obviously higher in herg-transfected A549 cells than in parent A549 cells. Erythromycin obviously suppressed the growth of HT-29 cells, and showed synergic cytotoxicity with doxorubicin to HT-29 cells. There is no difference in intracellular doxorubicin content among herg-transfected A549 cells, pCDNA3.1-transfected A549 cells, and parent A549 cells.

CONCLUSIONS:

HERG expression might negatively correlate with the chemosensitivity of tumor cells to doxorubicin. Erythromycin may act as a modulator, and has synergic effect with doxorubicin. HERG may serve as a molecular marker and modulating target for individualized cancer therapy.

PMID:
16086867
[Indexed for MEDLINE]

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