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血根碱与顺铂联用对膀胱癌EJ细胞凋亡的影响 被引量:2

Effect of sanguinarine combined with cisplatin on the apoptosis of bladder cancer EJ cells
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摘要 探讨血根碱与顺铂联用对膀胱癌EJ细胞凋亡的影响。应用CCK-8法检测不同浓度血根碱处理膀胱癌EJ细胞并计算IC_(50);应用Annexin V FITC/PI法检测空白对照组、血根碱组、顺铂组及联合用药组对细胞凋亡的影响应用;流式仪检测细胞周期阻滞情况;Western blot检测联合用药组对Bcl-2表达的影响;构建裸鼠皮下成瘤模型,进一步验证联合用药组对膀胱癌EJ细胞凋亡以及对荷瘤小鼠减毒作用的影响;同时,通过对小鼠重要脏器的HE染色评估血根碱的安全性。结果表明,血根碱能明显抑制EJ细胞增殖,与空白对照组相比,联合用药组EJ细胞凋亡显著(P<0.05),且更多的EJ细胞被阻滞在G_(2)/M期,联合用药组显著下调Bcl-2的表达(P<0.001)。裸鼠皮下成瘤模型中,同空白对照组相比,联合用药组中小鼠肿瘤生长明显变缓,细胞凋亡明显增加(P<0.05)。联合用药对荷瘤小鼠有减轻顺铂副作用的效果,血根碱的生物安全性高,副作用小。实验结果表明,血根碱与顺铂联合用药可通过引起细胞G_(2)/M阻滞,下调Bcl-2的表达,促进细胞凋亡,进而抑制肿瘤生长。 To investigate the effects of sanguinarine(Sang)combined with cisplatin(Cis)in accelerating the apoptosis of bladder cancer EJ cells,CCK-8 method was used to detect the proliferation of bladder cancer EJ cells treated with different concentrations of Sang with the IC_(50) values calculated.Annexin V FITC/PI method was used to detect cell apoptosis in the control group,Sang group,Cis group and the combination group.Flow cytometer was used to detect cell cycle arrested.Western blot was used to detect the influence of Bcl-2 expression in the control group,Sang group,Cis group and the combination group.Nude mouse subcutaneous tumor model was constructed to verify that the combination group could accelerate the apoptosis of bladder cancer EJ cells and reduce the side-effects on mice.The safety of the Sang was evaluated by HE staining of vital organs in mice.In vitro,Sang could significantly inhibit the proliferation of EJ cells.Compared with the control group,the number of apoptosis EJ cells in the combination group was significantly increased(P<0.05),and more cells were arrested in G_(2)/M phase.The expression of Bcl-2 was significantly down-regulated in the combination group(P<0.001).In vivo,compared with the control group,the tumor growth was significantly slower,and a large number of apoptotic cells were inspected(P<0.05)of the combination group.The side effects of cisplatin were reduced in the combination group.Sang has high biosafety and little side effect.Combined Sang and Cis can increase cell cycle G_(2)/M block,down-regulate Bcl-2 expression,promote cell apoptosis and inhibit tumor growth.
作者 石达 雷崎方 陶涛 马文龙 叶水仙 李广志 孙海燕 吴松 SHI Da;LEI Qifang;TAO Tao;MA Wenlong;YE Shuixian;LI Guangzhi;SUN Haiyan;WU Song(Medical College of Anhui University of Science and Technology,Huainan 232000;The Third Affiliated Hospital of Shenzhen University,Shenzhen 518000;The Following Precision Medicine Research Institute,Shenzhen 518000,China)
出处 《中国药科大学学报》 CAS CSCD 北大核心 2021年第4期463-471,共9页 Journal of China Pharmaceutical University
基金 国家重点研发计划资助项目(No.2017YFA0105900) 国家自然科学基金资助项目(No.81922046) 广东省医学科学技术研究基金资助项目(No.B2019016) 深圳市“医疗卫生三名工程”资助项目(No.SZSM201601043)。
关键词 血根碱 顺铂 膀胱癌 凋亡 联合用药 sanguinarine cisplatin bladder cancer apoptosis combination medication
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