灯盏乙素、灯盏乙素苷元及四乙酰灯盏乙素苷元联合三氧化二砷对乳腺癌细胞的增殖抑制作用研究

Study of Scutellarin,Scutellarein and Tetraacetyl Scutellarein Combined with Arsenic Trioxide on Breast Cancer Cell Proliferation Inhibition

目的探讨灯盏乙素及其衍生物和三氧化二砷单独及联合用药对乳腺癌细胞的作用。方法将体外培养的乳腺癌MDA-MB-231细胞分成对照组和用药组,每组设6个复孔。用药组为灯盏乙素及其衍生物(灯盏乙素苷元与四乙酰灯盏乙素苷元)单独用药,以及与5μM三氧化二砷一起联合用药。用MTT法测试它们对乳腺癌MDAMB-231细胞的抑制作用。结果灯盏乙素单独用药时,剂量为10μmol·L^(-1)、50μmol·L^(-1)、100μmol·L^(-1)时,对MDAMB-231细胞的抑制率分别为(0.01±5.56)%、(18.18±3.46)%、(35.72±5.27)%;灯盏乙素与5μM As_2O_3联合用药时,抑制率分别为(13.55±3.54)%、(32.6±5.09)%、(35.29±6.96)%。灯盏乙素苷元单独用药时,剂量为10μmol·L^(-1)、50μmol·L^(-1)、100μmol·L^(-1)时,对MDA-MB-231细胞的抑制率分别为(1.13±5.46)%、(1.68±6.55)%、(3.86±5.51)%;与5μM As_2O_3联合用药时,抑制率分别为(17.90±2.41)%、(28.13±4.63)%、(34.94±2.41)%。四乙酰灯盏乙素苷元单独用药时,剂量为1μmol·L^(-1)、5μmol·L^(-1)、10μmol·L^(-1)时,对MDA-MB-231细胞的抑制率分别为(0.76±5.07)%、(1.34±4.07)%、(-0.40±7.59)%;与5μM As_2O_3联合用药时,抑制率分别为(16.52±5.91)%、(17.25±3.89)%、(13.62±7.24)%.结论单独用药时,灯盏乙素对MDA-MB-231细胞的抑制作用大于灯盏乙素苷元及四乙酰灯盏乙素,糖基的去除和乙酰化使其作用减弱;与三氧化二砷联用时,灯盏乙素及灯盏乙素苷元对细胞有显著的抑制作用。其中,灯盏乙素苷元单独使用无抑制活性,却能显著增强三氧化二砷对细胞的抑制作用。灯盏乙素苷元与三氧化二砷联合用药具有治疗乳腺癌的应用前景。

Objective To investigate the effects of scutellarin and its derivatives on breast cancer cells and the synergistic anti-tumor effects of scutellarin and its derivatives combined with arsenic trioxide. Methods Human breast cancer MDA-MB-23 cells were＇ cultured in vitro and divided into control and test groups. Every group was set 6 wells. Test groups were treated with scutellarin and its derivatives alone and combined with 5μM arsenic trioxide. One of the derivatives of scutellarin is scutellarein, which is the glycone of scutellarin. Scutellarein is also the main metabolism product of scutellarin in vivo. The other derivatives of scutellarin is tetraacetyl scutellarein, which we synthesized to improve the low bioavailability of scutellarin. Inhibition of MDA-MB-23 ceils proliferation was tested by MTS assays. Results Scutellarin alone inhibited cell proliferation in a dose-dependent manner, when scutellarein and tetraacetylscutellarein showed slight inhibition effect. It indicated that the glucuronic acid moiety of scutellarin played an important part in cell proliferation inhibition. Both scutellarin and scutellarein combined with arsenic trioxide exerted synergistic effects on proliferation inhibition in MDA-MB-231 cells in dose-dependent manners. Particularly, scutellarein did not inhibit cell proliferation alone but significantly enhance the proliferation inhibition of arsenic trioxide on MDA-MB-231 cells. Conclusion The combination of scutellarein and arsenic trioxide inhibits breast cancer development more effectively than each drug alone.