Shu-Zhen Chen1, Min Jiang, Yong-su Zhen. 1. Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China, zhenys@public.bta.net.cn.
Abstract
PURPOSE: Previous studies have found that the HERG K+ channel is highly expressed in some cancers. In the study reported here, we investigated HERG expression in various cancer cell lines, its correlation with chemosensitivity to vincristine, paclitaxel, and hydroxy-camptothecin, and its biochemical modulation. METHODS: The MTT assay and clonogenic assay were used to detect the cytotoxicity of anticancer drugs in vitro. HERG expression was analyzed by Western blotting or immunocytochemistry. Gene transfection was used to examine the changes in HERG-related chemosensitivity. Cell cycle phase distribution was detected by flow cytometry and drug combinations were evaluated by the MTT assay. RESULTS: HERG expression levels differed widely between various human cancer cell lines and HT-29 cells expressing high levels of HERG were more sensitive than A549 cells expressing low levels of HERG to vincristine, paclitaxel, and hydroxy-camptothecin. In terms of IC50, the chemosensitivities of herg-transfected A549 cells to vincristine, paclitaxel and hydroxy-camptothecin were significantly increased. However, for cisplatin and 5-fluorouracil, no significant difference between herg-transfected A549 cells and parent A549 cells was detected. Erythromycin, a HERG K+ channel blocker, suppressed the growth of various cancer cells and the potency was correlated with HERG expression levels. Combinations of erythromycin and vincristine, paclitaxel or hydroxy-camptothecin showed synergy in cytotoxicity to HT-29 cells. Erythromycin also enhanced the G2/M arrest induced by vincristine in HT-29 cells. There were synergistic effects between erythromycin and vincristine, paclitaxel, and hydroxy-camptothecin, and chemosensitivity was correlated with HERG expression level. CONCLUSIONS: HERG expression levels and chemosensitivity were positively correlated for vincristine, paclitaxel, and hydroxy-camptothecin. Erythromycin was active as a modulator. These results suggest that HERG may serve as a molecular marker and modulating target for individualized cancer therapy.
PURPOSE: Previous studies have found that the HERG K+ channel is highly expressed in some cancers. In the study reported here, we investigated HERG expression in various cancer cell lines, its correlation with chemosensitivity to vincristine, paclitaxel, and hydroxy-camptothecin, and its biochemical modulation. METHODS: The MTT assay and clonogenic assay were used to detect the cytotoxicity of anticancer drugs in vitro. HERG expression was analyzed by Western blotting or immunocytochemistry. Gene transfection was used to examine the changes in HERG-related chemosensitivity. Cell cycle phase distribution was detected by flow cytometry and drug combinations were evaluated by the MTT assay. RESULTS:HERG expression levels differed widely between various humancancer cell lines and HT-29 cells expressing high levels of HERG were more sensitive than A549 cells expressing low levels of HERG to vincristine, paclitaxel, and hydroxy-camptothecin. In terms of IC50, the chemosensitivities of herg-transfected A549 cells to vincristine, paclitaxel and hydroxy-camptothecin were significantly increased. However, for cisplatin and 5-fluorouracil, no significant difference between herg-transfected A549 cells and parent A549 cells was detected. Erythromycin, a HERG K+ channel blocker, suppressed the growth of various cancer cells and the potency was correlated with HERG expression levels. Combinations of erythromycin and vincristine, paclitaxel or hydroxy-camptothecin showed synergy in cytotoxicity to HT-29 cells. Erythromycin also enhanced the G2/M arrest induced by vincristine in HT-29 cells. There were synergistic effects between erythromycin and vincristine, paclitaxel, and hydroxy-camptothecin, and chemosensitivity was correlated with HERG expression level. CONCLUSIONS:HERG expression levels and chemosensitivity were positively correlated for vincristine, paclitaxel, and hydroxy-camptothecin. Erythromycin was active as a modulator. These results suggest that HERG may serve as a molecular marker and modulating target for individualized cancer therapy.
Authors: Torsten K Roepke; Kerry Purtell; Elizabeth C King; Krista M D La Perle; Daniel J Lerner; Geoffrey W Abbott Journal: PLoS One Date: 2010-07-06 Impact factor: 3.240
Authors: Carla Maria P Ribeiro; Harry Hurd; Yichao Wu; Mary E B Martino; Lisa Jones; Brian Brighton; Richard C Boucher; Wanda K O'Neal Journal: PLoS One Date: 2009-06-05 Impact factor: 3.240