CAJ | 학술논문

目的探讨多激酶抑制剂索拉非尼单药及与二甲双胍联合给药时,对甲状腺未分化癌细胞的作用及其机制.方法采用细胞培养技术,以流式细胞术、Western印迹等方法,在索拉非尼单药或与二甲双胍联合给药后,观察细胞生长、细胞周期及凋亡、caspase-3活性以及细胞外信号调节激酶(ERK)磷酸化的变化.结果索拉非尼抑制甲状腺未分化癌细胞生长,干预48 h后,索拉非尼对SW1736和C643的EC50分别为3.68 μmol/L和4.87 μmol/L;阻断细胞周期于G0/1期,S期细胞显著减少；诱导细胞凋亡,索拉非尼、索拉非尼+二甲双胍作用后,SW1736细胞caspase3活性分别为131.5％、278.0％(P＜0.01),C643细胞caspase3活性分别为127.2％、196.6％ (P＜0.01).分子水平,索拉非尼抑制ERK蛋白磷酸化.二甲双胍可协同索拉非尼抑制肿瘤细胞生长,2.5 μmol/L索拉非尼、2.5 μmol/L索拉非尼+5 mmol/L二甲双胍作用后,SW1736细胞活力为0.76±0.17、0.30 ±0.04(P＜0.01),C643分别为0.72±0.09、0.34±0.10(P＜0.001).结论多激酶抑制剂索拉非尼和二甲双胍联合用药可成为临床上治疗甲状腺未分化癌及其他进展期肿瘤的有效策略.
목적 탐토다격매억제제색랍비니단약급여이갑쌍고연합급약시,대갑상선미분화암세포적작용급기궤제.방법 채용세포배양기술,이류식세포술、Western인적등방법,재색랍비니단약혹여이갑쌍고연합급약후,관찰세포생장、세포주기급조망、caspase-3활성이급세포외신호조절격매(ERK)린산화적변화.결과 색랍비니억제갑상선미분화암세포생장,간예48 h후,색랍비니대SW1736화C643적EC50분별위3.68 μmol/L화4.87 μmol/L;조단세포주기우G0/1기,S기세포현저감소；유도세포조망,색랍비니、색랍비니+이갑쌍고작용후,SW1736세포caspase3활성분별위131.5％、278.0％(P＜0.01),C643세포caspase3활성분별위127.2％、196.6％ (P＜0.01).분자수평,색랍비니억제ERK단백린산화.이갑쌍고가협동색랍비니억제종류세포생장,2.5 μmol/L색랍비니、2.5 μmol/L색랍비니+5 mmol/L이갑쌍고작용후,SW1736세포활력위0.76±0.17、0.30 ±0.04(P＜0.01),C643분별위0.72±0.09、0.34±0.10(P＜0.001).결론 다격매억제제색랍비니화이갑쌍고연합용약가성위림상상치료갑상선미분화암급기타진전기종류적유효책략.
Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers.