Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Pathol Oncol Res. 2010 Jun;16(2):229-37. doi: 10.1007/s12253-009-9215-4. Epub 2009 Oct 12.
Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.
Pim-2 被证实与肝细胞癌（HCC）的发生有关，但具体机制尚不清楚。本研究旨在探讨 Pim-2、NF-κB 与 API-5 之间的关系。本实验检测了 HCC 组织及相应癌旁组织中 Pim-2、NF-κB 及 API-5 的表达水平、API-5 磷酸化水平及 NF-κB 活性，并在正常肝细胞 L02 中转染 Pim-2 基因，在肝癌细胞 HepG2 中转染 Pim-2 SiRNA，同时给予 NF-κB 抑制剂白屈菜碱（Parthenolide），重复上述检测并进行细胞凋亡分析。结果发现 HCC 组织中 Pim-2、NF-κB 及 API-5 的表达水平及 NF-κB 活性明显高于癌旁组织，Pim-2 基因转染 L02 细胞后 Pim-2 表达水平增加，而 Pim-2 SiRNA 转染 HepG2 细胞后 Pim-2 表达水平降低，NF-κB 及 API-5 的表达水平及 NF-κB 活性、API-5 磷酸化水平与 Pim-2 表达水平变化一致，Parthenolide 可逆转上述变化，细胞凋亡率与 API-5 磷酸化水平呈负相关。由此我们推断 Pim-2 可能通过激活 API-5 抑制肝细胞凋亡，而 NF-κB 是其关键调控因子。
