Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1α pathway in human ovarian cancer in vitro.
Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1α pathway in human ovarian cancer in vitro.
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琥珀酸脱氢酶 B 亚基在体外抑制人卵巢癌中的 AMPK-HIF-1α 通路
DOI：
10.1186/s13048-014-0115-1
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发表时间：
2014-12-10
影响因子：
4
通讯作者：
Di W
中科院分区：
文献类型：
--
作者：
Chen L;Liu T;Zhang S;Zhou J;Wang Y;Di W
背景：卵巢癌是妇科最常见的恶性肿瘤之一，死亡率高。大量证据表明，肿瘤细胞在肿瘤发生过程中，在肿瘤微环境中发生代谢异常，进而促进肿瘤的进展。琥珀酸脱氢酶（SDH或复合物II）是三羧酸（TCA）循环中的重要酶之一。琥珀酸脱氢酶亚单位B（SDHB）基因编码琥珀酸脱氢酶（SDH）的四个亚单位之一，被认为是一种肿瘤抑制因子。方法：利用SDHB特异性siRNA和过表达质粒，分别在卵巢癌细胞株SKOV 3和A2780中沉默和反向诱导SDHB的表达。SDHB在卵巢癌中的可能作用进行了研究，在体外，使用增殖，迁移和侵袭试验。Western blot检测Bcl-2、caspase 3、p-ERK、MMP-2、p-FAK等细胞增殖和迁移相关蛋白的表达。Western blot检测P-P38、p-AMPKα和HIF-1α的表达。结果：SDHB沉默可促进SKOV 3和A2780细胞的增殖、侵袭和迁移，但抑制SKOV 3和A2780细胞的凋亡。相反，SDHB的过表达抑制SKOV 3细胞的增殖、侵袭、迁移，并促进细胞凋亡。SDHB沉默后，Bcl-2和MMP-2表达上调，p-P38、p-ERK和p-FAK激活，caspase 3活性降低。SDHB过表达的SKOV 3细胞Bcl-2和MMP-2表达降低，p-P38、p-ERK和p-FAK表达抑制，caspase 3激活。HIF-1α是肿瘤进展中的一个重要因子，在SDHB沉默的细胞中随着p-AMPKα的激活而上调，在SDHB过表达的癌细胞中随着p-AMPKα的降低而下调。结论：SDHB通过AMPK-HIF-1α途径参与卵巢癌细胞的增殖、侵袭、迁移和凋亡。SDHB过表达可能是抑制卵巢癌进展的新途径。
Background:Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Numerous evidences demonstrate that cancer cells undergo metabolic abnormality during tumorigenesis in tumor microenvironment and further facilitate tumor progression. Succinate dehydrogenase (SDH or Complex II) is one of the important enzymes in the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been recognized as a tumor suppressor. However the role of SDHB in ovarian cancer is still unclear.Methods:Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer was investigated in vitro, using proliferation, migration and invasion assays. To explore the mechanism, proliferation and migration related proteins such as Bcl-2, cleaved caspase 3, p-ERK, MMP-2, and p-FAK were examined by western blot. P-P38, p-AMPKα, and HIF-1α were also examined by western blot. CoCl2 was used to induce HIF-1α expression in SKOV3 and A2780 cells.Results:SDHB silencing promoted cell proliferation, invasion, and migration, but inhibited apoptosis of SKOV3 and A2780 cells. In contrast, overexpression of SDHB inhibited cell proliferation, invasion, migration, and promoted apoptosis in SKOV3 cells. It was observed that up-regulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK, and p-FAK, inhibition of cleaved caspase 3 in SDHB-silenced cells. Meanwhile, decreased Bcl-2 and MMP-2, inhibition of p-P38, p-ERK, and p-FAK, activation of cleaved caspase 3 were shown in SDHB-overexpressed SKOV3 cells. HIF-1α, an essential factor in tumor progression, was up-regulated in SDHB-silenced cells with the activation of p-AMPKα and down-regulated in SDHB-overexpressed cancer cells with the decreased p-AMPKα. And SDHB was proved to be decreased due to upregulation of HIF-1α expression in CoCl2-treated cancer cells.Conclusions:Our results firstly revealed that SDHB played a key role in cell proliferation, invasion, migration, and apoptosis of human ovarian carcinoma via AMPK-HIF-1α pathway. SDHB-overexpression might be a new approach to inhibit tumor progression in human ovarian carcinoma.
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DOI：
10.1038/modpathol.2010.185
发表时间：
2011-01
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.3
作者：
Karna, Ewa;Szoka, Lukasz;Palka, Jerzy
通讯作者：
Palka, Jerzy
影响因子：
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作者：
Brentnall M;Rodriguez-Menocal L;De Guevara RL;Cepero E;Boise LH
通讯作者：
Boise LH
DOI：
10.3322/caac.20113
发表时间：
2011-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Jelovac D;Armstrong DK
通讯作者：
Armstrong DK
DOI：
10.1016/j.bbagen.2013.06.004
发表时间：
2013-10-01
影响因子：
3
作者：
Hsu, Chia-Chi;Wang, Chun-Hui;Lee, Hsin-Chen
通讯作者：
Lee, Hsin-Chen