目的探讨川陈皮素对乳腺癌细胞MDA-MB-231的体外化疗增敏作用。方法以MDA-MB-231细胞为研究对象,MTT法测定细胞增殖抑制率,DNALadder、核小体双抗体ELISA和流式细胞仪测定MDA-MB-231细胞凋亡情况,凝胶阻滞实验(EMSA)和ELISA检测川陈皮素对核转录因子(NF-κB)的转录激活的影响。结果20μmol/L川陈皮素分别与1nmol/L紫杉醇或50ng/mL阿霉素联合使用肿瘤细胞增殖抑制率为75.1%和82.6%,单独使用1nmol/L紫杉醇或50ng/mL阿霉素肿瘤细胞增殖抑制率为40%和45%;核小体双抗体夹心酶免疫法和DNA凝胶电泳实验表明川陈皮素与紫杉醇或阿霉素联合用药可明显促进MDA-MB-231细胞的凋亡,EMSA和ELISA实验表明川陈皮素与紫杉醇或阿霉素联合用药可明显抑制NF-κB的转录活性。结论川陈皮素可以促进临床化疗药物对乳腺癌细胞增殖的抑制作用和诱导凋亡作用,其机制可能是通过抑制NF-κB转录作用。

Objective To investigate whether nobiletin could enhance chemotherapeutic drug-induced cell proliferation inhibition and apoptosis in breast carcinoma cells MDA-MB-231 in vitro.Methods MDA-MB-231 cells were exposed to nobiletin and different chemotherapeutic drugs at different concentration.The cell proliferation inhibitory rate was observed by MTT,apoptosis was detected by DNA Ladder,flow cytometry (FCM),and ELISA,and an NF-κB electrophoretic mobility shift was conducted by EMSA and ELISA.Results The combination of nobiletin (20 μmol) with Taxol (1 nmol) or Doxorubicin (50 ng/mL) resulted in a significant inhibitory rate of cell growth and more apoptosis in MDA-MB-231 cells of 75.1% and 82.6% compared with either of them alone (40% and 45%),respectively.DNA Ladder and FCM assay showed that nobiletin could promote the cell apoptosis induced by chemotherapeutic drug.EMSA and ELISA assay showed that nobiletin could inhibit NF-κB activity in nuclear and cytoplasm of MDA-MB-231 cells.Conclusion The current results suggest that nobiletin could enhance the inhibition of chemotherapeutic drug on cell proliferation and cell apoptosis of breast carcinoma cells MDA-MB-231,the mechanism may be related to down-regulate the NF-κB activity in vitro.

国家自然科学基金资助项目(30701098)