水飞蓟素对乳腺癌细胞系的作用及其机制研究

Inhibitory effect of silymarin on different breast cancer cell lines and associated molecular mechanism

目的 研究水飞蓟素在体外对不同乳腺癌细胞系的作用 ,并进一步探讨其作用机制。方法 MTT实验测定水飞蓟素对乳腺癌细胞系 MCF- 7和 SK- BR- 3的半数抑制浓度 ( IC50 ) ;软琼脂克隆形成试验检测加药后两种细胞在软琼脂内的增殖能力。在此基础上 ,用 Her- 2抑制剂 AG82 5进行干预 ,对水飞蓟素的作用机制进行初步探讨。结果 水飞蓟素对两种乳腺癌细胞有不同程度的抑制作用 ,其中对 MCF- 7细胞的作用较强 ,IC50 ≤ 0 .0 2 %,而对SK- BR- 3的作用较弱。 Her- 2抑制剂 AG82 5可增加 SK- BR- 3细胞对药物的敏感性 ,抑制了水飞蓟素作用后该细胞在软琼脂中集落的形成。结论 水飞蓟素在体外对 MCF- 7细胞具有明显的抑制作用 ,而 AG82 5可增强 SK- BR-3细胞对药物的敏感性。因此 ,SK- BR- 3细胞中 Her- 2的高表达可能是该细胞对水飞蓟素敏感性差的原因 ,而水飞蓟素也可能通过 Her- 2调节某个或某几个下游分子起作用。

Object To investigate the anticancer effect of silymarin on different breast cancer cell lines, and approach the molecular mechanism. Methods Two breast cancer cell lines were cultured to study the effect of silymarin on cell growth and proliferation. Firstly, MTT assay was used to evaluate the IC 50 of silymarin on the two cell lines, MCF-7 and SK-BR-3. Secondly, through soft agar assay, the ability of cell proliferation, when exposed to silymarin at various dosages, was detected. Finally, AG825, inhibitor of the protein tyrosine kinase Her-2 was used to intervene the effect of silymarin on SK-BR-3 cells. Results Silymarin could inhibit the growth of MCF-7 and SK-BR-3 cells in vared degrees. MCF-7 cells were very sensitive to the agent, IC 50≤0.02%; while SK-BR-3 cells were less sensitive. Her-2 inhibitor AG825 increased the sensitivity of SK-BR-3 cells to silymarin and inhibited the growth of the cells in soft agar. Conclusion From the above, it could be concluded that silymarin has the cancer chemopreventive and anticancer effects on breast cancer cell lines. It could completely inhibit the growth of MCF-7 cells, and partly of SK-BR-3 cells. AG825 could improve the sensitivity of SK-BR-3 cells to silymarin. Overexpression of Her-2 on the surface of SK-BR-3 cells may be owed to the lower sensitivity to silymarin and silymarin may be possible to affect cell growth through one or more downstream molecules regulated by Her-2.ari