摘要
目的探讨归芪白术方联合奥沙利铂通过PI3K/Akt/caspase-9通路对荷瘤小鼠的抑瘤作用及细胞凋亡的机制。方法建立荷瘤模型,随机分模型组、奥沙利铂组(10 mg·kg^(-1))、奥沙利铂+归芪白术方高、中、低剂量组(17.68、8.84、4.42 g·kg^(-1));末次给药后切除移植瘤,计算抑制率;苏木精-伊红染色法(HE)观察瘤组织病理改变;免疫组化法(IHC)检测p-PI3K、p-Akt、caspase-9、caspase-3表达;免疫印迹法(Western blot)检测Bax、Bcl-2及PI3K/Akt/caspase-9通路表达情况。结果各用药组瘤重较模型组降低(P<0.01);与奥沙利铂组比,奥沙利铂+归芪白术方高、中剂量组瘤重降低(P<0.05,P<0.01);模型组肿瘤细胞密集,未见组织坏死区;各用药组肿瘤细胞减少,有明显的组织坏死区和广泛炎性细胞浸润;与模型组比,各给药组p-PI3K、p-Akt、Bcl-2蛋白下降,而caspase-9、cleaved-caspase-9、caspase-3、cleaved-caspase-3、Bax蛋白升高;与奥沙利铂组比,奥沙利铂+归芪白术方高剂量组p-PI3K、p-Akt、Bcl-2蛋白下降(P<0.05,P<0.01),caspase-9、cleaved-caspase-9、caspase-3、cleaved-caspase-3、Bax升高(P<0.05,P<0.01);奥沙利铂+归芪白术方中剂量组p-PI3K、p-Akt蛋白下降(P<0.05),cleaved-caspase-9和Bax含量升高(P<0.05)。结论归芪白术方可提高奥沙利铂抑瘤作用,促进胃癌细胞凋亡,其机制可能与PI3K/Akt/caspase-9信号通路有关。
Aim To investigate the inhibitory effect of Guiqi Baizhu recipe combined with oxaliplatin on tumor bearing rats and the molecular mechanism of cell apoptosis through PI3K/Akt/caspase-9 pathway.Methods Model of gastric cancer was established and the rats were randomly divided into model group,oxaliplatin group(10 mg·kg^(-1)),oxaliplatin+Guiqi Baizhu recipe high-dose,medium-dose and low-dose groups(17.68,8.84,4.42 g·kg^(-1)).The graft tumor was resected after the last administration,and the graft tumor inhibition rate was calculated.HE staining was used to observe the pathological changes of tumor tissue.The expression of p-PI3K,p-Akt,caspase-9 and caspase-3 proteins were detected by IHC.The expression of apoptosis related proteins Bax,Bcl-2 and PI3K/Akt/caspase-9 pathway were detected by Western blot.Results Compared with the model group,the weight of tumor in each administration group was lower(P<0.01).Compared with the oxaliplatin group,the weight of tumor in the high-dose and medium-dose groups was lower(P<0.05,P<0.01).The tumor cells in model group were dense,and no tissue necrosis area was observed.The tumor cells in each treatment group decreased,and there was obvious tissue necrosis area and extensive inflammatory cell infiltration.Compared with the model group,the expression of p-PI3K,p-Akt and Bcl-2 in each administration group decreased,while the expressions of caspase-9,cleaved-caspase-9,caspase-3,cleaved-caspase-3 and Bax increased.Compared with oxaliplatin group,the expression of p-PI3K,p-Akt and Bcl-2 in high-dose group decreased(P<0.05,P<0.01).However,the expression of caspase-9,cleaved-caspase-9,caspase-3,cleaved-caspase-3,and Bax increased(P<0.05,P<0.01).The expression of p-PI3K,p-Akt in medium-dose group decreased(P<0.05);the expression of cleaved-caspase-9,cleaved-caspase-3,and Bax increased(P<0.05).Conclusions Guiqi Baizhu recipe can improve the tumor inhibition effect of oxaliplatin and promote apoptosis of gastric cancer cells,and its mechanism may be related to the regulation of PI3K/Akt/c
作者
黄勇
张晗
龚红霞
刘永琦
董焕成
陈红纲
房明
吴国泰
苏韫
HUANG Yong;ZHANG Han;GONG Hong-xia;LIU Yong-qi;DONG Huan-cheng;CHEN Hong-gang;FANG Ming;WU Guo-tai;SU Yun(School of Basic Medicine,Gansu University of Chinese Medicine;Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities;Key Laboratory of TCM Prevention and Treatment of Chronic Diseases in Gansu Provincial;Key Laboratory of Gastrointestinal Cancer Diagnosis and Treatment of National Health Commission,Gansu Provincial People's Hospital,Lanzhou 730000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第9期1781-1786,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81660744)
胃肠肿瘤诊治重点实验室开放基金(No NLDTG2020013)
中西医结合学科2021年度"双一流"科研重点项目(No GSSYLXM-05)
甘肃中医药大学研究生创新创业基金(No 2022CX07)。
