摘要
AIM: JS-38(mitothiolore), a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell(WBC) elevating activities. METHOD: These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide(CTX) or 5-fluorouracil(5-Fu) were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. RESULTS: The IC50 values ranged from 0.1 to 2.0 μmol·L-1. JS-38(1 μmol·L-1) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38(15, 30, and 60 mg?kg-1?d-1) inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor(G-CSF). In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. CONCLUSION: These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
AIM： JS-38（mitothiolore）, a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell（WBC） elevating activities. METHOD： These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide（CTX） or 5-fluorouracil（5-Fu） were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. RESULTS： The IC50 values ranged from 0.1 to 2.0 μmol·L-1. JS-38（1 μmol·L-1） caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38（15, 30, and 60 mg？kg-1？d-1） inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor（G-CSF）. In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. CONCLUSION： These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
基金
supported by the National Natural Science Foundation of China(No.30973639)
the Biomedicine Scientific and Technological Projects of Shanghai(#1043 1900700)
