目的 研究芒柄花苷对乳腺癌细胞MCF-7增殖、凋亡和侵袭的影响及作用机制。方法 采用不同浓度芒柄花苷处理乳腺癌细胞MCF-7,噻唑盐(MTS)染色检测细胞活力,EdU检测细胞增殖能力,Hoechst染色法检测细胞凋亡,Transwell小室实验检测细胞侵袭和迁移能力,Western-blotting检测增殖细胞核抗原(PCNA)、凋亡相关蛋白(Bax和Bcl-2)和基质蛋白酶(MMP)-9的表达。结果 芒柄花苷剂量和时间依赖性的抑制MCF-7细胞的生长。MCF-7细胞经芒柄花苷干预后,EdU阳性细胞数减少、侵袭及迁移细胞数减少和Hoechst阳性细胞数增加。芒柄花苷作用MCF-7细胞,可上调Bax的表达和下调Bcl-2、PCNA和MMP-9的表达。结论 芒柄花苷可抑制乳腺癌细胞MCF-7的增殖、诱导凋亡和减少侵袭,其机制可能分别涉及调节PCNA、Bcl-2/Bax和MMP-9的表达。
Abstract
OBJECTIVE To investigate the anti-breast cancer effect of ononin and its mechanism in vitro. METHODS After treating with different concentration of ononin, the MCF-7 cells viability was determined by MTS, EdU and Hoechst were used to measure the proliferative ability and apoptotic rate of MCF-7, respectively. The invasion and migration of MCF-7 were determined by Transwell assays. The protein expression including PCNA, apoptosis-related proteins (Bax and Bcl-2) and MMP-9 were evaluated by Western-blotting. RESULTS Ononin inhibited the cells viability of MCF-7 in a dose-and time-dependent manner. The EdU positive cells were decreased, Hoechst positive cells were increased, invasive and migration cells were decreased after treating with ononin in MCF-7. Moreover, ononin up-regulated Bax expression and down-regulated Bcl-2, PCNA as well as MMP-9 expression. CONCLUSION Ononin could inhibit the MCF-7 cells proliferation, promote cells apoptosis, decrease cells invasion and migration, which may involve the regulative effect on PCNA, Bax /Bcl-2 and MMP-9 expression.
关键词
芒柄花苷 /
乳腺癌 /
MCF-7
{{custom_keyword}} /
Key words
ononin /
breast cancer /
MCF-7
{{custom_keyword}} /
中图分类号：
R737.9
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] ZHU Y N, LI L, ZHOU N, et al. Analysis of drug-induced liver injury in clinical pathway on patients with breast cancer and colorectal cancer [J]. Chin Pharm J (中国药学杂志), 2018, 53 (14):1230-1233.
[2] ZHANG W, JIANG S H, QIAN D W, et al. The interaction between ononin and human intestinal bacteria [J]. Acta Pharm Sin(药学学报), 2014, 49 (8):1162-1168.
[3] ZHOU R, CHEN H, CHEN J, et al. Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway [J]. BMC Complement Altern Med, 2018, 18(1):83.
[4] ZHANG L H, WU T T, ZHAO L G, et al. Advances in studies on anticancer activity of flavonoids from Ginkgo biloba extract [J]. Chin Pharm J (中国药学杂志), 2019, 54(6):444-449.
[5] PANG B B, CHU Y K, YANG H. Anti-breast cancer mechanism of flavonoids [J]. China J Chin Mater Med (中国中药杂志), 2018, 43(5):913-920.
[6] SOUZA P O, BIANCHI S E, FIGUEIRO F, et al. Anticancer activity of flavonoids isolated from Achyrocline satureioides in gliomas cell lines [J]. Toxicol In Vitro, 2018, 51: 23-33.
[7] MATEEVA N, EYUNNI S V K, REDDA K K, et al. Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties [J]. Bioorg Med Chem Lett, 2017, 27(11):2350-2356.
[8] WANG Y, LI Y, ZHANG Y, et al. Multi-dimensional spectrum-effect relationship of the impact of chinese herbal formula lichong shengsui yin on ovarian cancer [J]. Molecules, 2017, 22(6):pii: E979.
[9] HE X R, HAN S Y, LI X H, et al. Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of non-small cell lung cancer via inhibition of transforming growth factor β1 signaling pathway in vitro and in vivo [J]. J Ethnopharmacol, 2017, 204: 45-57.
[10] JURIKOVA M, DANIHEL, POLAK , et al. Ki67, PCNA, and MCM proteins: markers of proliferation in the diagnosis of breast cancer[J]. Acta Histochem, 2016, 118(5):544-552.
[11] KALE J, OSTERLUND E J, ANDREWS D W. BCL-2 family proteins: changing partners in the dance towards death [J]. Cell Death Differ, 2018, 25(1):65-80.
[12] ADAMS J M, CORY S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets [J]. Cell Death Differ, 2018, 25(1):27-36.
[13] HUANG H. Matrix metalloproteinase-9(MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances [J]. Sensors (Basel), 2018, 18(10):pii: E3249.
[14] YANG J, MIN K W, KIM D H, et al. High TNFRSF12A level associated with MMP-9 overexpression is linked to poor prognosis in breast cancer: gene set enrichment analysis and validation in large-scale cohorts [J]. PLoS One, 2018, 13(8):e0202113.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
甘肃省自然科学基金资助(18JR3RA352)
{{custom_fund}}
PDF(2112 KB)
