Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay

基于中空纤维法评价狼毒提取物的抗肿瘤药理作用

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作者:Xiaoni Liu, Qing Yang, Ganlin Zhang, Yujie Li, Ying Chen, Xiaogang Weng, Yajie Wang, Yiwei Wang, Xiaoxin Zhu

Background

Stellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo.

Conclusion

ESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

Methods

In this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively.

Results

The results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment.

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