A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leukemia cells.
A novel combination of oridonin and valproic acid in enhancement of apoptosis induction of HL-60 leukemia cells.
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冬凌草甲素和丙戊酸的新型组合可增强 HL-60 白血病细胞的凋亡诱导。
DOI：
10.3892/ijo.2015.3294
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发表时间：
2016-02
影响因子：
5.2
通讯作者：
Jiang Guosheng
中科院分区：
文献类型：
--
作者：
Shi Meiyan;Ren Xia;Wang Xidi;Wang Hengxiao;Liu Guoqiang;Yuan Xiaofen;Zheng Shubo;Yu Linchang;Pan Sufei;Song Guanhua;Guo Qiang;Li Lianlian;Zhang Xiaoyu;Zhang Zhiyong;Ding Huifang;Jiang Guosheng
从中草药冬凌草中提取的冬凌草素对肿瘤细胞具有较强的抗肿瘤活性。丙戊酸（VPA）作为一种有效的组蛋白去乙酰化酶抑制剂（HDACI），在抑制肿瘤细胞增殖方面也发挥着重要作用。然而，目前尚无关于冬凌草甲素与VPA协同抗白血病作用的报道。因此，在本研究中，我们进行了实验，以确定较低浓度的冬凌草甲素与较低浓度的VPA联合使用是否会产生比单独使用更令人鼓舞的协同效应，并阐明其分子机制。结果表明，较低浓度的冬甲素联合较低浓度的VPA协同抑制HL-60细胞的增殖，并通过激活Bcl-2/Bax比值下调、细胞色素c向胞浆释放、caspase-9活化等内源性凋亡途径，以及Fas/FasL和caspase-8活化介导的外源性凋亡途径诱导明显的caspase依赖性凋亡。此外，MAPK信号通路也参与了冬凌草苷+ VPA诱导的细胞凋亡。此外，在体内，联合治疗显著减少了异种移植肿瘤的大小，并引发肿瘤细胞凋亡。综上所述，冬凌草甲素与VPA的新组合对人髓系白血病细胞具有协同的抗增殖和诱导凋亡作用，可能是一种潜在的有前景的抗白血病策略。
Oridonin, obtained from the traditional Chinese herbal medicine rabdosia rubescens, exerts potent antitumor activities in cancer cells. Valproic acid (VPA), as a potent histone deacetylase inhibitor (HDACI), also plays an important role in inhibition of proliferation of tumor cells. However, there are no reports so far on the cooperation between oridonin and VPA for anti-leukemic effect. Therefore, in the present study, we undertook experiments to determine whether lower concentration of oridonin in conjunction with lower concentration of VPA would produce even more encouraging synergistic effect than each of them alone, and to clarify its molecular mechanism. The results demonstrated that the lower concentration of oridonin in combination with lower concentration of VPA synergistically inhibited the proliferation of HL-60 cells, and induced obvious caspase-dependent apoptosis through activation of the intrinsic apoptosis pathway, which is involved in the downregulation of Bcl-2/Bax ratio, release of cytochrome c to cytosol and caspase-9 activation, as well as through the extrinsic apoptosis pathway mediated by Fas/FasL and caspase-8 activation. In addition, MAPK signaling pathway was also involved in apoptosis induced by oridonin plus VPA. Furthermore, the combination treatment in vivo remarkably reduced the xenograft tumor size and triggered tumor cell apoptosis. Taken together, the novel combination of oridonin plus VPA exerted synergistic anti-proliferative and apoptosis-inducing effects on human myeloid leukemia cells, and may serve as a potential promising anti-leukemia strategy.
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急性早幼粒细胞白血病的治疗
DOI：
10.1007/978-3-030-72676-8_8
发表时间：
2021
期刊：
Acute Myeloid Leukemia
影响因子：
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作者：
S. Kayser;U. Platzbecker
通讯作者：
U. Platzbecker
DOI：
10.4084/mjhid.2012.012
发表时间：
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
3.6
作者：
Jin, Song;Shen, Jing-nan;Zhou, Jia-Guo
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冬凌草甲素与三氧化二砷对肝癌细胞的协同抗肿瘤活性
影响因子：
5.2
作者：
Chen, Guo;Wang, Ke;Hua, Zi-Chun
通讯作者：
Hua, Zi-Chun