博来霉素联合顺铂对人胃癌细胞的体外抗癌作用研究  

Anticancer effect of bleomycin combined with cisplatin on human gastric cancer cells in vitro

作　　者：杨孜[1] 崔永辉[1] 李知翰 郑紫恒 张西亮[1] 高慧洁 Yang Zi;Cui Yonghui;Li Zhihan;Zheng Zhiheng;Zhang Xiliang;Gao Hujie(Department of Gastroenterology,Shangqiu First People's Hospital,Shangqiu 476000,China;Department of Gastroenterology,the First Affiliated Hospital of Henan University,Kaifeng 475000,China)

机构地区：[1]河南省商丘市第一人民医院消化内科,商丘476000 [2]河南大学第一附属医院消化内科,开封475000

出　　处：《中华内分泌外科杂志》2023年第4期474-479,共6页Chinese Journal of Endocrine Surgery

基　　金：河南省科技公关项目(LHGJ20200542)。

摘　　要：目的为探索博来霉素(bleomycin,Ble)联合顺铂(cisplatin,DDP)后对人胃癌细胞的体外抗癌效果。方法CCK-8实验检测博来霉素和顺铂单独及联用对胃癌细胞的增殖的影响,流式细胞术检测细胞凋亡的变化和活性氧水平的变化,细胞划痕实验检测细胞迁移;Westernblot实验检测蛋白表达。结果CCK-8结果显示20μMDDP对6种胃癌细胞的增殖抑制率为40%,20μMBle则只有20%左右,当两者混合使用以10μMBle+10μMDDP处理后,对6种胃癌细胞的抑制率能达到60%以上,其中对AGS细胞的抑制效果最强。10μMBle+10μMDDP联合处理时AGS凋亡细胞比例达到75.68%,高于两种药物分别以20μM处理时的诱导调亡效果。10μMBle+10μMDDP联合使用时迁移及侵袭的细胞数目显著降低,抑制率达到50%,与20μMDDP单独使用相比,差异具有统计学意义(P<0.05)。流式细胞术结果表明博来霉素与顺铂联用能通过上调细胞中活性氧的水平促进癌细胞凋亡;Western blot结果表明博来霉素与顺铂联用后p-JAK2和p-STAT3的表达量降低,抑制JAK2/STAT3信号通路。结论博来霉素与顺铂联用能抑制胃癌细胞的增殖和迁移,促进胃癌细胞的凋亡,协同发挥抗癌作用,其作用机制可能是通过上调细胞中ROS水平,进而抑制JAK2/STAT3通路的激活。Objective To explore the in vitro anticancer effect of bleomycin(Ble)combined with cisplat-in(DDP)on human gastric cancer cells.Methods CCK-8 experiment was conducted to detect the effect of Ble and DDP alone or in combination on the proliferation of gastric cancer cells;Flow cytometry was used to detect changes in cell apoptosis and changes in reactive oxygen species.Cell scratch test was employed to detect cell mi-gration;Western blot experiment was conducted to detect protein expression.Results The results of CCK-8 showed that 20μM DDP could inhibit the proliferation of six types of gastric cancer cells by 40%,while the effect of 20μM Ble was only about 20%.When used in combination,the inhibitory rate on six types of gastric cancer could reach over 60%,with the strongest inhibitory effect on AGS cells.When 10μM Ble and 10μM DDP were combined,the proportion of ACS apoptotic cells reached 75.68%,higher than that of the two drugs treated with 20%,respectively 20μM processing effect.When 10μM Ble and 10μM DDP were used in combination,the num-ber of migrating and invading cells was significantly reduced,and the inhibition rate reached 50%.Compared with single use,the difference was statistically significant(P<0.05).Flow cytometry results showed that the combina-tion of Ble and DDP promoted cancer cell apoptosis by up-regulating the level of reactive oxygen species in cells;Western blot results showed that the expression of p-JAK2 and p-STAT3 decreased after Ble and DDP were com-bined,indicating that the JAK2/STAT3 signal pathway was inhibited.Conclusions The combination of Ble and DDP can inhibit the proliferation and migration of gastric cancer cells,promote the apoptosis of gastric cancer cells,and play a synergistic anti-cancer effect,Its mechanism may be related to the up-regulation of ROS levels in cells,thereby inhibiting the activation of the JAK2/STAT3 pathway.

关 键 词：博来霉素 顺铂 胃癌 活性氧 JAK2/STAT3通路 

分 类 号：R735.2[医药卫生—肿瘤]