赵虹,沃立科,胡袁媛,等.黄连素抑制GRP78表达促进三阴乳腺癌细胞凋亡的研究[J].浙江中医药大学学报,2019,43(5):407-412. |
黄连素抑制GRP78表达促进三阴乳腺癌细胞凋亡的研究 |
Berberine Promotes Apoptosis of Triple-Negative Breast Cancer Cells by Inhibiting GRP78 Expression |
DOI:10.16466/j.issn1005-5509.2019.05.004 |
中文关键词: 三阴乳腺癌 黄连素 葡萄糖调节蛋白78 细胞凋亡 细胞增殖 免疫球蛋白重链结合蛋白诱导剂X |
英文关键词: triple-negative breast cancer berberine GRP78 cell apoptosis cell proliferation immunoglobulin heavy chain binding protein inducer X |
基金项目:国家自然科学基金项目(81703368);浙江省自然科学基金项目(LY16H300003) |
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中文摘要: |
[目的]通过检测黄连素对三阴乳腺癌(triple-negative breast cancer,TNBC)细胞株MDA-MB-231细胞凋亡及葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)表达的影响,探讨黄连素抗TNBC的机制。[方法]以MTT法检测不同浓度黄连素对MDA-MB-231细胞增殖的影响,筛选黄连素的处理浓度。将MDA-MB-231细胞分为对照组、40μmol·L-1黄连素组、60μmol·L-1黄连素组、免疫球蛋白重链结合蛋白诱导剂X(immunoglobulin heavy chain binding protein inducer X,BiX)组,以及BiX联合40μmol·L-1黄连素组、BiX联合60μmol·L-1黄连素组。相应药物处理24h后,应用流式细胞术检测细胞凋亡情况,并以Western blot检测细胞GRP78和凋亡相关基因Bcl-2、Bax的表达。[结果]40μmol·L-1以上浓度的黄连素可剂量依赖性抑制MDA-MB-231细胞增殖。与对照组比较,BiX组细胞凋亡率降低(P<0.05)、GRP78和Bcl-2表达增高(P<0.01,P<0.001)、Bax表达减低(P<0.05)。与BiX组比较,BiX联合40、60μmol·L-1黄连素组细胞凋亡率增加(P<0.01),GRP78和Bcl-2表达减低(P<0.01,P<0.01),Bax表达增加(P<0.01)。[结论]黄连素可以促进MDA-MB-231细胞凋亡,其机制可能是通过下调 GRP78的表达,从而降低Bcl-2表达,并促进Bax的表达。 |
英文摘要: |
[Objective] To explore the mechanism of berberine against triple-negative breast cancer(TNBC) by detecting the effect of berberine on the apoptosis of MDA-MB-231 cell and the expression of glucose regulated protein 78(GRP78) in MDA-MB-231 cells.[Methods] To screen the concentration of berberine, MTT assay was used to detect the effect of different concentrations of berberine on the proliferation of MDA-MB-231 cells. MDA-MB-231 cells were cultured and divided into control group, 40μmol·L-1 berberine group, 60μmol·L-1 berberine group, immunoglobulin heavy chain binding protein inducer X(BiX) group, BiX combined 40μmol·L-1 berberine group and BiX combined 60μmol·L-1 berberine group. After 24h of treatment, apoptosis of MDA-MB-231 cells was detected by flow cytometry, and Western blot was used to detect the expression of GRP78 and apoptosis-related genes Bcl-2 and Bax. [Results] Berberine, which was more than 40μmol·L-1, could inhibit the proliferation of MDA-MB-231 in a dose-dependent manner. Compared with control group, the apoptotic rate of BiX group decreased (P<0.05), while the expression of GRP78 and Bcl-2 increased (P<0.01, P<0.001), and the expression of Bax decreased(P<0.05). Compared with BiX group, the apoptotic rate of BiX combined 40/60μmol·L-1 berberine group increased(P<0.01), while the expression of GRP78 and Bcl-2 decreased(P<0.01, P<0.01), and the expression of Bax increased(P<0.01). [Conclusion] Berberine can promote the apoptosis of MDA-MB-231 cells by down-regulating the expression of GRP78, thus inhibiting the expression of Bcl-2 and promoting the expression of Bax. |
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