Alpinetin suppresses proliferation of human hepatoma cells by the activation of MKK7 and elevates sensitization to cis-diammined dichloridoplatium.
Alpinetin suppresses proliferation of human hepatoma cells by the activation of MKK7 and elevates sensitization to cis-diammined dichloridoplatium.
复制标题
Alpinetin 通过激活 MKK7 抑制人肝癌细胞的增殖，并提高对顺式二氨二氯化铂的敏感性。
DOI：
10.3892/or.2011.1580
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发表时间：
2012-04
期刊：
影响因子：
4.2
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Tang B;Du J;Wang J;Tan G;Gao Z;Wang Z;Wang L
山姜素是从草豆蔻中提取的一种新型黄酮类化合物，具有较强的抗肝癌作用。然而，Alpinetin的抗肿瘤机制仍不清楚。丝裂原活化蛋白激酶激酶-7（MKK 7）可调节细胞的生长、分化和凋亡。本研究的目的是探讨MKK 7在Alpinetin介导的抗肝癌作用中的作用。采用RT-PCR和Western blotting方法检测不同浓度Alpinetin作用HepG 2细胞不同时间后磷酸化MKK 7（p-MKK 7）和总MKK 7的表达水平。瞬时转染RNA干扰后，采用甲基噻唑基四氮唑法和流式细胞仪测定细胞活力和细胞周期，以评价Alpinetin的抗肿瘤作用。此外，通过细胞计数阵列评价Alpinetin对顺铂（CDDP）的化学增敏作用，并计算细胞生长抑制率。结果表明，山姜素通过上调p-MKK 7的表达水平，抑制HepG 2细胞增殖，使细胞阻滞于G 0/G1期。抑制MKK 7的表达可逆转Alpinetin的抗肿瘤作用。此外，山姜素增强HepG 2肝癌细胞对化疗药物顺铂的敏感性。综上所述，我们的研究表明MKK 7的活化介导了Alpinetin的抗肝癌作用。MKK 7可能是肝癌分子治疗的一个潜在靶点，Alpinetin可能成为肝癌治疗的潜在药物。
Alpinetin is a type of novel plant flavonoid derived from Alpinia katsumadai Hayata, found to possess strong anti-hepatoma effects. However, the detailed antitumor mechanism of Alpinetin remains unclear. Mitogen-activated protein kinase kinase-7 (MKK7) can regulate cellular growth, differentiation and apoptosis. The aim of this study was to investigate the role of MKK7 in the anti-hepatoma effect mediated by Alpinetin. HepG2 cells were treated with Alpinetin at various doses and for different times, and the levels of phosphorylated MKK7 (p-MKK7) and total MKK7 were tested by RT-PCR and Western blotting. Following transient transfection with RNA interference, cell viability and cell cycle stage were determined using methyl thiazolyl tetrazolium assay and flow cytometry, in order to assess the antitumor action of Alpinetin. In addition, chemosensitization to cis-diammined dichloridoplatium (CDDP) by Alpinetin was assessed by cell counting array and the cell growth inhibitory rate was calculated. The results showed that Alpinetin suppressed HepG2 cell proliferation and arrested cells in the G0/G1 phase by up-regulating the expression levels of p-MKK7. On the contrary, inhibiting the expression of MKK7 reversed the antitumor effect of Alpinetin. Moreover, Alpinetin enhanced the sensitivity of HepG2 hepatoma cells to the chemotherapeutic agent CDDP. Taken together, our studies indicate that activation of MKK7 mediates the anti-hepatoma effect of Alpinetin. MKK7 may be a putative target for molecular therapy against hepatoma and Alpinetin could serve as a potential agent for the development of hepatoma therapy.
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影响因子：
37.3
作者：
Mondal S;Mandal C;Sangwan R;Chandra S;Mandal C
通讯作者：
Mandal C
DOI：
10.1017/s1461145711000897
发表时间：
2012-07-01
影响因子：
4.8
作者：
Galeotti, Nicoletta;Ghelardini, Carla
通讯作者：
Ghelardini, Carla
影响因子：
4.1
作者：
Suzuki, A;Guicheux, J;Caverzasio, J
通讯作者：
Caverzasio, J
DOI：
10.1002/lt.20034
发表时间：
2004-02-01
期刊：
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
影响因子：
--
作者：
Llovet, Josep M;Fuster, Josep;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M