21种香豆素类化合物体外抑制鼻咽癌活性的研究

Screening of 21 Coumarins Antitumor Activity of Nasopharyngeal Carcinoma in Vitro

目的探讨21种香豆素类化合物体外抑制鼻咽癌细胞的增殖及诱导其凋亡的活性。方法运用CCK-8法和台盼蓝染色法测定21种香豆素类化合物对鼻咽癌细胞CNE-2和HONE-1体外半数抑制浓度及半数致死浓度,随后利用Annexin VFITC/PI染色法检测药物处理后细胞凋亡率的变化。结果 21种香豆素类化合物中,对鼻咽癌细胞半数抑制浓度最低的3个化合物为蛇床子素、白花前胡甲素及秦皮乙素,对CNE-2细胞的半数抑制浓度分别为(44.8±5.2)μmol/L、(72.3±9.8)μmol/L和(129.6±8.9)μmol/L;在HONE-1细胞中的半数抑制浓度分别是(38.6±6.3)μmol/L、(45.3±8.4)μmol/L和(62.7±7.0)μmol/L。同时,上述3个化合物也是半数致死浓度最低的3个化合物,对CNE-2细胞的半数抑制浓度分别为(62.4±6.9)μmol/L、(93.2±13.5)μmol/L和(129.2±11.5)μmol/L;在HONE-1细胞中的半数抑制浓度分别是(49.6±5.6)μmol/L、(83.2±7.3)μmol/L和(92.5±14.6)μmol/L。而21种香豆素化合物中,蛇床子素、白花前胡甲素、秦皮乙素、佛手柑内酯和欧前胡素能显著诱导鼻咽癌细胞凋亡(凋亡率>50%)。结论蛇床子素、白花前胡甲素及秦皮乙素具有较为显著的体外抑制鼻咽癌细胞增殖及诱导其凋亡的活性。

OBJECTIVE To investigate the effect of coumarins antitumor activity of nasopharyngeal carcinoma（ NPC） cells in vitro.METHODS The inhibition were testing by CCK-8 and trypan blue staining,when the NPC cells＇ CNE-2 and HONE-1 exposed to coumarins for 48 h in different concentration. The apoptosis rate was measured by FACSCanto II flow cytometer using Annexin VFITC / PI staining.RESULTS The top 3 activity coumarins were osthole,praeruptorin A,and esculetin. In CNE-2 cells,the half maximal inhibitory concentration（ IC50） of osthole,praeruptorin A,and esculetin were（ 44.8±5.2） μmol/L,（ 72.3±9.8） μmol/L,and（ 129.6±8.9） μmol / L; the half maximal lethal concentration（ LC50） of osthole,praeruptorin A,and esculetin were（ 62.4±6.9）μmol /L,（ 93.2±13.5） μmol /L,and（ 129.2± 11.5） μmol /L. In HONE-1 cells,the IC50 of osthole,praeruptorin A,and esculetin were（ 38.6±6.3） μmol / L,（ 45.3±8.4） μmol / L,and（ 62.7± 7.0） μmol / L; the LC50 of osthole,praeruptorin A,and esculetin were（ 49.6±5.6） μmol/L,（ 83.2±7.3） μmol/L,and（ 92.5±14.6） μmol/L. The Osthole,Praeruptorin A,Esculetin,Bergapten,and Imperatorin remarkably induced apoptosis in CNE-2 and HONE-1 cells. CONCLUSION These results highlight that osthole,praeruptorin A,and esculetin exert effects of antiproliferative and inducing apoptosis in NPC cells.