摘要
目的:探究重楼皂苷Ⅱ对胶质瘤增殖,侵袭及耐药性的作用及机制。方法:CCk-8法检测不同浓度重楼皂苷Ⅱ对胶质瘤细胞系T98G和LN18增殖的影响。Transwell小室实验检测不同浓度重楼皂苷Ⅱ对胶质瘤细胞系T98G和LN18侵袭能力的影响。Western印迹法检测E-cadherin、Snail和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)表达。结果:重楼皂苷Ⅱ能抑制胶质瘤细胞系T98G和LN18的增殖,且随着浓度的增加和时间的延长抑制作用更强。T98G 24、48和72 h的IC 50分别为(5.82±0.32)、(3.57±0.07)、(1.48±0.35)μmol/L。LN1824、48和72 h的IC 50分别为(6.83±0.11)、(4.28±0.29)、(2.66±0.22)μmol/L。T98G和LN18分别以2、4和6μmol/L重楼皂苷Ⅱ处理24 h后,侵袭细胞面积占小室面积的百分比明显低于T98G和LN18以0μmol/L重楼皂苷Ⅱ处理24 h后的百分比,差异具有统计学意义(P<0.05)。Western印迹实验检测发现与未经重楼皂苷Ⅱ处理的胶质瘤细胞相比,T98G与LN18中E-cadherin的表达较高(F=85.56,P<0.05;F=60.80,P<0.05),Snail的表达较低(F=25.34,P<0.05;F=48.28,P<0.05)。不同浓度替莫唑胺与重楼皂苷Ⅱ联合使用时,药物相互作用系数(CDI)均<1,Western印迹检测发现与未经重楼皂苷Ⅱ处理的胶质瘤细胞相比,T98G与LN18中MGMT的表达受抑制(F=40.38,P<0.05;F=48.44,P<0.05)。结论:重楼皂苷Ⅱ能抑制胶质瘤的增殖、侵袭并提高对替莫唑胺的敏感性。
Objective To investigate the effect and mechanism of PolyphyllinⅡon the proliferation,invasion and chemosensitivity of glioma cells.Method CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of PolyphyllinⅡon the proliferation and invasion of glioma cells(T98G and LN18),respectively.The expression of E-cadherin,Snail and O6-methylguanine DNA methyltranferase(MGMT)were quantified by Western blot analysis.Results PolyphyllinⅡcould inhibit the proliferation of glioma cells in a time-and does-dependent manner.The half maximal inhibitory concentration(IC50)of T98G at 24 h,48 h and 72 h were(5.82±0.32),(3.57±0.07)and(1.48±0.35)µmol/L,respectively.The IC50 of LN18 at 24 h,48 h and 72 h were(6.83±0.11),(4.28±0.29),(2.66±0.22)µmol/L,respectively.After being treated with 2µmol/L,4µmol/L and 6µmol/L PolyphyllinⅡfor 24 h,the percentage of invasive cell area in the chamber area was lower than those in T98G and LN18 control groups(P<0.05).Western blot analysis showed that compared with glioma cells without PolyphyllinⅡtreatment,the expression of E-cadherin in T98G and LN18 was higher(F=85.56,P<0.05;F=60.80,P<0.05),but the expression of snail was lower(F=25.34,P<0.05;F=48.28,P<0.05).When temozolomide was used in combination with PolyphyllinⅡat different concentrations,the coefficient of drug interaction(CDI)was less than 1.Western blot showed that MGMT expressions in T98G and LN18 were inhibited compared with glioma cells without PolyphyllinⅡtreatment(F=40.38,P<0.05;F=48.44,P<0.05).Conclusion PolyphyllinⅡcan inhibit the proliferation and invasion of glioma cells,and improve its sensitivity to Temozolomide.
作者
赵亚鹏
段文超
王艳敏
张振宇
刘献志
Zhao Yapeng;Duan Wenchao;Wang Yanmin;Zhang Zhenyu;Liu Xianzhi(Department of Neurosurgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2020年第35期2774-2778,共5页
National Medical Journal of China
基金
国家自然科学基金 (81702465,U1804172)。