HERG K～+ Channel Expression Related Chemosensitivity In Cancer Cells And The Study On Pharmacokinetics Of Lidamycin

1. HERG K⁺ channel expression related chemosensitivity in cancer cells and its modulation by erythromycinherg encodes a particular type of K⁺ channel (HERG) belonging to an evolutionary conserved multi-gene family of voltage-activated, outward rectifying K⁺ channels, the eag family. As known, HERG channels are tetramers, with each subunit consisting of six transmembrane domains (denoted S1-S6), and both N and C termini are located intracellularly. herg and its related current are preferentially expressed in neoplastic cell lines of different histogenesis. Furthermore, HERG channels are involved in the regulation of cell proliferation and apoptosis. However, there are no reports on the correlation of HERG expression and chemosensitivity in cancer cells.There is increasing evidence that ion channels, such as Ca²⁺ and K⁺ channels, play a key role in modulation of cell cycle. Calcium channel blockers have shown to inhibit cell growth and metastasis in various models of neoplasia and potentiate the antiproliferative activity of some anticancer drugs. Moreover, some potassium channel blockers have been reported to exert growth inhibition of several kinds of cancer cells or display synergistic effects in combination with anticancer drugs. Ion channels have become potential molecular targets for modulation of chemosensitivity in cancer therapy. As reported, erythromycin which is a macrolide antibiotic shows a concentration-dependent inhibition of the herg-encoded potassium current. Apparently, erythromycin may serve as a K⁺ channel blocker. In the present study, we demonstrate that HERG K⁺ channel expression is related to the chemosensitivity in cancer cells and erythromycin acts as a modulator for the effect of chemotherapeutic agents.HERG expression level was highly diverse in various human cancer cell lines by Western blot analysis. In all of the tested human cancer cell lines, the level of HERG...