Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice  

作　　者：Yong-zhan ZHEN Ya-jun LIN Yi LI Yong-su ZHEN 

机构地区：[1]Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050, China [2]North China Coal Medical College, Tangshan 063000, China

出　　处：《Acta Pharmacologica Sinica》2009年第7期1025-1032,共8页中国药理学报（英文版）

摘　　要：Aim： To investigate the effects of lidamycin （LDM） on a mouse myeloma cell line （SP2/0） and human multiple myeloma cell lines （U266 and SKO-007）, and provide the basis for the use of LDM in cancer therapy. Methods： A 3-[4,5-dimethylthiazol-2-yl]5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]2H-tetrazolium inner salt （MTS） assay was used to determine the degree of growth inhibition by the drugs analyzed in this study. Cell cycle distribution and analysis were measured by flow cytometry combined with propidium iodide （PI） staining. The effects on apoptosis were measured by Hoechst 33342 staining and by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide （FITC-Annexin V/PI） staining. Protein expression was determined by Western blot analysis. In vivo antitumor activity was measured using a murine myeloma model in BALB/c mice. Results： There was a significant reduction in cell proliferation after treatment with LDM. The overall growth inhibition correlated with increased apoptotic cell death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N-terminal kinase （JNK）, and cleavage of caspase-3/7 and poly （ADP-ribose） polymerase （PARP）. LDM markedly suppressed tumor growth in a murine myeloma model. Conclusion： LDM induces apoptosis in murine myeloma SP2/0 cells as well as in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice. Taken together, our data provide some clues for further research of the effects of LDM on human multiple myeloma.Aim： To investigate the effects of lidamycin （LDM） on a mouse myeloma cell line （SP2/0） and human multiple myeloma cell lines （U266 and SKO-007）, and provide the basis for the use of LDM in cancer therapy. Methods： A 3-[4,5-dimethylthiazol-2-yl]5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]2H-tetrazolium inner salt （MTS） assay was used to determine the degree of growth inhibition by the drugs analyzed in this study. Cell cycle distribution and analysis were measured by flow cytometry combined with propidium iodide （PI） staining. The effects on apoptosis were measured by Hoechst 33342 staining and by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide （FITC-Annexin V/PI） staining. Protein expression was determined by Western blot analysis. In vivo antitumor activity was measured using a murine myeloma model in BALB/c mice. Results： There was a significant reduction in cell proliferation after treatment with LDM. The overall growth inhibition correlated with increased apoptotic cell death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N-terminal kinase （JNK）, and cleavage of caspase-3/7 and poly （ADP-ribose） polymerase （PARP）. LDM markedly suppressed tumor growth in a murine myeloma model. Conclusion： LDM induces apoptosis in murine myeloma SP2/0 cells as well as in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice. Taken together, our data provide some clues for further research of the effects of LDM on human multiple myeloma.

关 键 词：LIDAMYCIN mouse myeloma multiple myeloma JNK SP2/0 cells 

分 类 号：Q26[生物学—细胞生物学] X592[环境科学与工程—环境工程]