目的探讨小檗碱对人乳腺癌细胞MDA-MB-23体外生长的影响及其与过氧化物酶体增殖物激活受体γ(PPARγ)的关系,以评价其在乳腺癌治疗中的应用潜力。方法采用MTT法检测小檗碱对MDA-MB-23细胞的生长抑制效应;TUNEL法检测细胞凋亡;联合PPARγ拮抗剂GW9662,分析小檗碱对MDA-MB-23细胞增殖的影响与PPARγ受体的关系;实验同时采用罗格列酮作为阳性药进行平行比较分析。结果小檗碱呈量-效和时-效关系抑制MDA-MB-23细胞生长,24h的半数抑制浓度(IC50)为0.2μmol/L;小檗碱诱导MDA-MB-23细胞凋亡作用随药物浓度的增加而增强;PPARγ受体拮抗剂不能逆转小檗碱对细胞增殖的抑制作用。结论小檗碱可明显抑制MDA-MB-23细胞生长,但与罗格列酮不同,其作用不通过PPARγ受体介导;小檗碱诱导MDA-MB-23细胞凋亡的效应较罗格列酮更为显著;小檗碱可望成为治疗乳腺癌的有效药物。

Objective To investigate the anti-tumor effects and its relationship to peroxisome proliferator-activated receptor γ (PPARγ) of berberine on human breast cancer cell line MDA-MB-231 in order to evaluate the potential application value of berberine for breast cancer therapy. Methods Cytostatic effects of berberine on MDA-MB-231 cells were measured by MTT assay. Apoptotic cells were determined by Tunel assay. MDA-MB-231 Cells were treated with berberine alone or in combination with PPARγ antagonist GW9662 to investigate the effects of berberine on the cells proliferation and its relationship to PPARγ. Results MTT Analysis detected that berberine could inhibit the growth of MDA-MB-231 cells in a concentration and time-dependent manner with IC50 values of 0.21 μmol/L at 24 h after the drug added into the culture. Apparent apoptosis of MDA-MB-231 cells induced by berberine was observed and the apoptotic rates could be going up with the concentration of berberine increased. The inhibitory effect of berberine on cell proliferation could not be reversed by PPARγ selective antagonist GW9662. Conclusion In addition to inhibiting of MDA-MB-231 cells growth which was independent of PPARγ, berberine can also induce the cells' apoptosis which suggests that berberine might be an effective and promising agent for the treatment of breast cancer.

国家自然科学基金资助项目(30572353)