This study is to investigate inhibitory effects of
lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing
cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of
lidamycin combined with various anticancer drugs on the proliferation of human
lung cancer A549 cells, human
colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of
drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG
potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of
fluorouracil (5-FU) and LDM,
doxorubicin (DOX) and LDM, or hydroxycamptothecine (
HCPT) and LDM. CDI values of the combinations of
5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and
HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and
HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of
cancer cells by
5-FU and HERG
potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of
cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for
HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or
HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and
HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of
cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and
HCPT, which inhibitory effects of the proliferation of
cancer cells positively modulated by HERG
potassium expression level. HERG K+ channel may become a target of combined
therapy for choosing anticancer drugs.