中国药理学通报
中國藥理學通報
중국약이학통보
Chinese Pharmacological Bulletin
2015年
11期
1592-1597
,共6页
钌%抗肿瘤%肝癌%细胞凋亡%信号转导通路%caspas-es
釕%抗腫瘤%肝癌%細胞凋亡%信號轉導通路%caspas-es
조%항종류%간암%세포조망%신호전도통로%caspas-es
ruthenium%anticancer%hepatocellular carcinoma%cell apoptosis%signaling pathways%caspas-es
目的探讨钌多吡啶配合物的体内外抗肝癌活性及其作用机制。方法 MTT 法筛选出高效低毒的钌配合物2b；流式细胞术分析其对细胞周期的影响；Western blot法检测p53和p21蛋白的表达水平；荷瘤裸鼠实验评价该配合物的体内抗肿瘤活性。结果钌多吡啶配合物对多种人肝癌细胞株的生长有抑制作用,其中配合物2b对肝癌细胞Hep 3B的作用最明显,IC50为12.1μmol·L-1。2b可以有效地诱导Hep 3B细胞凋亡,使细胞内出现了DNA断裂,染色质固缩及subG1凋亡峰的出现。同时,2b能够激活 caspase-9和caspase-3,促使p53蛋白磷酸化,提高 p53总蛋白和 p21蛋白的表达水平。体内实验表明,配合物2b对裸鼠肿瘤的生长有明显的抑制作用。结论钌多吡啶配合物在体内外模型中均具有良好的抗肝癌活性,通过诱导肿瘤细胞凋亡而抑制其增殖。
目的探討釕多吡啶配閤物的體內外抗肝癌活性及其作用機製。方法 MTT 法篩選齣高效低毒的釕配閤物2b；流式細胞術分析其對細胞週期的影響；Western blot法檢測p53和p21蛋白的錶達水平；荷瘤裸鼠實驗評價該配閤物的體內抗腫瘤活性。結果釕多吡啶配閤物對多種人肝癌細胞株的生長有抑製作用,其中配閤物2b對肝癌細胞Hep 3B的作用最明顯,IC50為12.1μmol·L-1。2b可以有效地誘導Hep 3B細胞凋亡,使細胞內齣現瞭DNA斷裂,染色質固縮及subG1凋亡峰的齣現。同時,2b能夠激活 caspase-9和caspase-3,促使p53蛋白燐痠化,提高 p53總蛋白和 p21蛋白的錶達水平。體內實驗錶明,配閤物2b對裸鼠腫瘤的生長有明顯的抑製作用。結論釕多吡啶配閤物在體內外模型中均具有良好的抗肝癌活性,通過誘導腫瘤細胞凋亡而抑製其增殖。
목적탐토조다필정배합물적체내외항간암활성급기작용궤제。방법 MTT 법사선출고효저독적조배합물2b；류식세포술분석기대세포주기적영향；Western blot법검측p53화p21단백적표체수평；하류라서실험평개해배합물적체내항종류활성。결과조다필정배합물대다충인간암세포주적생장유억제작용,기중배합물2b대간암세포Hep 3B적작용최명현,IC50위12.1μmol·L-1。2b가이유효지유도Hep 3B세포조망,사세포내출현료DNA단렬,염색질고축급subG1조망봉적출현。동시,2b능구격활 caspase-9화caspase-3,촉사p53단백린산화,제고 p53총단백화 p21단백적표체수평。체내실험표명,배합물2b대라서종류적생장유명현적억제작용。결론조다필정배합물재체내외모형중균구유량호적항간암활성,통과유도종류세포조망이억제기증식。
Aim To evaluate the antitumor activity of ruthenium polypyridyl complexes and the underlying mechanism. Methods The right complexes 2b were filtered with highest activity and lowest toxicity by MTT assay. The change of cell cycle was detected by flow cytometry . The expression of p53 and p21 was detected by Western blot. The in vivo antitumor activity of 2b was evaluated by the assay of tumor bearing nude mice. Results 2b potentially inhibited proliferation of a variety of hepatoma cell lines, among which Hep 3B cell was the most significant ( IC50 was 12. 1 μmol · L-1 ) . The apoptosis of Hep 3 B cell was induced by 2b, as evidenced by DNA fragmentation, chromatin condensation and appearance of subG1 peak. The ac-tivities of caspase-9 and caspase-3 were activated by 2b. The phosphorylation of p53 was induced by 2b. The expression of p53 and p21 was also up-regulated by 2b. The growth of tumor of nude mice was signifi-cantly inhibited by 2b in vivo experiment. Conclusion 2b has good in vitro and vivo antitumor activities, and it can inhibite growth of Hep 3 B cells by inducing apoptosis.
