| 朱丽华,徐刚,龚爱华,等.STAT3抑制剂Stattic对肝癌细胞Bel-7402生长、迁移、侵袭和放射敏感性的影响[J].中华放射医学与防护杂志,2015,35(6):413-418.Zhu Lihua,Xu Gang,Gong Aihua,et al.The effects of Stattic, a STAT3 inhibitor, on the growth, migration and radiosensitivity of liver cancer cells Bel-7402[J].Chin J Radiol Med Prot,2015,35(6):413-418 |
| STAT3抑制剂Stattic对肝癌细胞Bel-7402生长、迁移、侵袭和放射敏感性的影响 |
| The effects of Stattic, a STAT3 inhibitor, on the growth, migration and radiosensitivity of liver cancer cells Bel-7402 |
| 投稿时间：2014-12-24 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.06.003 |
| 中文关键词: Stattic 放射敏感性 肝癌细胞 细胞侵袭 细胞凋亡 |
| 英文关键词:Stattic Radiosensitivity Hepatocellular carcinoma cell Cell invasion Cell apoptosis |
| 基金项目:国家自然科学基金(81372718) |
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| 中文摘要: |
| 目的 观察信号转导子和转录激活子3(signal transducer and activator of transcription 3,STAT3)抑制剂Stattic(Y705)对人肝癌细胞系Bel-7402的生长、迁移、侵袭和放射敏感性的影响。方法 将人肝癌细胞系Bel-7402分为4组,空白对照组、Stattic组、单纯照射组和Stattic联合照射组(联合组)。CCK8检测细胞的生长和增殖;划痕愈合实验和Transwell侵袭实验分别检测各组细胞的迁移能力和侵袭能力;克隆形成实验观察Stattic对Bel-7402细胞放射敏感性的影响;Western blot检测各组STAT3、p-STAT3、Bax,Bcl-2、Caspase-3、Cleaved Caspase-3、MMP-2、MMP-9蛋白的表达水平。结果 Stattic明显抑制人肝癌Bel-7402细胞的生长,并表现出剂量-效应关系,Stattic作用于细胞48 h后的IC50为2.5 μmol/L。1.0 μmol/L的Stattic与8 Gy射线照射联用,两者在细胞增殖抑制率上,表现出协同作用,抑制率下降了(15.00±1.87)%(F=63.30,P<0.05)。划痕愈合实验显示联合组细胞的迁移能力明显降低,Transwell侵袭实验显示联合组滤膜细胞数明显减少。克隆形成实验显示,联合组与单纯照射组相比,克隆形成能力下降,SF2、D0、Dq均下降,(t=4.20、6.92、9.32,P<0.05)。Stattic在0.5 μmol/L时放射增敏比(SERSF2)为1.22。Western blot结果显示与单纯照射组相比,联合组的p-STAT3、MMP-2、MMP-9蛋白表达降低(t=5.32、6.02、13.26,P<0.05)。Bax、Cleaved Caspase-3蛋白表达升高(t=-7.82、-14.09,P<0.05)。Bcl-2蛋白的表达下降(t=18.43,P<0.05)。结论 Stattic通过抑制肝癌细胞Bel-7402的p-STAT3激活,一方面诱导凋亡增加肿瘤细胞的放射敏感性;另一方面降低了金属基质蛋白酶的上升,从而降低了肿瘤细胞迁移和侵袭能力。 |
| 英文摘要: |
| Objective To study the effects and preliminary mechanism of Stattic (Y705), an inhibitor of the signal transducer and activator of transcription-3 (STAT3), on the growth, migration, invasion and radiosensitization of hepatocellular carcinoma cell line Bel-7402. Methods Bel-7402 cells were divided to four groups: blank control group, Stattic treatment group, radiation group, and Stattic combined with radiation group. The cell growth and proliferation were detected by using CCK8 kit. The influence of Stattic on radiation sensitivity of Bel-7402 cells was determined by clone formation assay. The cell migration and invasion ability were tested by scratch migration assay and transwell assay, respectively. The protein expressions of STAT3, p-STAT3, Bax, Bcl-2, Caspase-3, Cleaved Caspase-3, MMP-2 and MMP-9 were quantified by Western blotting assay. Results Stattic significantly inhibited the growth of human hepatocellular carcinoma Bel-7402 cells with a dose-depended manner. The IC50 of Stattic after 48 h treatment was 2.5 μmol/L. When 1.0 μmol/L Stattic was combined with 8 Gy X-rays, there was a synergistic effect in inhibition of cell proliferation with a inhibition rate of (15.00±1.87) %(F=63.30,P<0.05). Scratch migration assay and transwell invasion assay showed that the migration and invasion abilities of the combination group were significantly reduced. In addition, compared with the radiation group, the SF2, D0 and Dq values obtained from survival curve were decreased (t=4.20,6.92,9.32,P<0.05),the protein expressions of p-STAT3,MMP-2,MMP-9 were reduced(t=5.32,6.02,13.26,P<0.05), the protein expressions of Bax and Cleaved Caspase-3 were increased in the combination group(t=-7.82,-14.09,P<0.05),meanwhile the protein expressions of Bcl-2 was decreased(t=18.43,P<0.05). When the concentration of Stattic was 0.5 μmol/L, the radiation sensitization ratio at 2 Gy (SERSF2) was 1.22. Conclusions By inhibiting the activation of the p-STAT3 in Bel-7402 cells, stattic could induce cell apoptosis and increase the radiosensitivity, down regulate MMP-2 and MMP-9 and thereby reduce the invasion and migration of tumor cells. |
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