Flavonoid compound breviscapine suppresses human osteosarcoma Saos-2 progression property and induces apoptosis by regulating mitochondria-dependent pathway.

Flavonoid compound breviscapine suppresses human osteosarcoma Saos-2 progression property and induces apoptosis by regulating mitochondria-dependent pathway.
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DOI:
10.1002/jbt.22633
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发表时间:
2021-01
影响因子:
3.6
通讯作者:
Liu Y
Liu Y
中科院分区:
医学4区
文献类型:
--
作者:
Wang Z;Li H;Yan J;Liu Y

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本研究旨在研究黄酮类化合物灯盏花素(BVP)抑制人骨肉瘤(OS)Saos-2细胞生长并诱导其凋亡的能力。在体外培养细胞,并用三种浓度的BVP(80、160和320 μg/ml)处理。此外,向C57小鼠注射Saos-2细胞以建立皮下异种移植模型,随后通过腹膜内注射给予三种剂量的BVP。通过细胞计数试剂盒-8方法检查细胞的活力。流式细胞术和末端脱氧核苷酸转移酶dUTP缺口末端标记法检测凋亡细胞。从最后一次注射后第3天至第21天监测肿瘤体积和重量。真实的荧光定量PCR检测bax、bcl-2和细胞色素c(cyt c)mRNA的表达。通过蛋白质印迹法检测Bax、bcl-2、cyt c、caspase 3和caspase 9的蛋白水平。免疫组化法检测bcl-2和bax在组织中的表达和分布。与对照组相比,BVP处理在体外抑制Saos‐2细胞的增殖并诱导其凋亡。一致地,用BVP处理荷移植肿瘤的小鼠抑制OS肿瘤的生长并促进细胞凋亡;它还减少肿瘤体积和重量。从机制上讲,BVP诱导的细胞凋亡是由线粒体依赖性途径介导的,如bax和cyt c表达增加和bcl-2表达减少以及体外和体外caspase 9和caspase 3活化所证明。总的来说,BVP通过激活线粒体凋亡途径抑制OS的生长并促进其凋亡。
This study was aimed to investigate the ability of a flavonoid compound breviscapine (BVP) to suppress growth and elicit apoptosis in human osteosarcoma (OS) Saos‐2 cells. The cells were cultured in vitro and treated with three concentrations of BVP (80, 160, and 320 μg/ml). Moreover, C57 mice were injected with Saos‐2 cells to establish a subcutaneous xenograft model, and they were subsequently treated with three doses of BVP via intraperitoneal injection. The viability of the cells was examined by the Cell Counting Kit‐8 method. The apoptotic cells were assessed by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The tumor volume and weight were monitored from day 3 through day 21 after the last injection. The expression of bax, bcl‐2, and cytochrome c (cyt c) mRNA was detected by a real‐time polymerase chain reaction. The protein levels of bax, bcl‐2, cyt c, caspase 3, and caspase 9 were evaluated by Western blot. The expression and distribution of bcl‐2 and bax in tissues were detected by immunohistochemistry. Compared with the control group, BVP treatment inhibited cell proliferation and induced apoptosis of Saos‐2 cells in vitro. Consistently, treatment of mice bearing transplanted tumors with BVP suppressed the growth of OS tumors and promoted cell apoptosis; it also reduced tumor volume and weight. Mechanistically, BVP‐induced apoptosis was mediated by the mitochondria‐dependent pathway, as evidenced by the increased expression of bax and cyt c and the decreased expression of bcl‐2, as well as activation of caspase 9 and caspase 3 in vitro and in vitro. Collectively, BVP inhibits growth and promotes apoptosis of OS by activating the mitochondrial apoptosis pathway.
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影响因子: 7.2
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发表时间: 2017-06
期刊: Cancer prevention research (Philadelphia, Pa.)
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