左卡尼汀联合表柔比星对不同肺腺癌细胞增殖及凋亡的影响  

Effects of cell proliferation and apoptosis of L-carnitine combined with epirubicin on different human lung adenocarcinoma cells

作　　者：叶因涛 仲巍[2] 钱钧强 石芸[3] 王晨 Ye Yintao;Zhong Wei;Qian Junqiang;Shi Yun;Wang Chen(Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China;Department of Quality, Tianjin Smith Kline & French Laboratories Ltd, Tianjin 300163, China;Department of Pharmacy, Tianjin Gongan Hospital, Tianjin 300042, China)

机构地区：[1]天津医科大学肿瘤医院药学部,国家肿瘤临床医学研究中心,天津市“肿瘤防治”重点实验室,天津市恶性肿瘤临床医学研究中心,300060 [2]中美天津史克制药有限公司质量部,天津300163 [3]天津市公安医院药剂科,300042

出　　处：《国际生物医学工程杂志》2019年第1期15-20,共6页International Journal of Biomedical Engineering

基　　金：天津市卫计委中医中西医结合科研课题(2015066,2017167).

摘　　要：目的研究左卡尼汀(LCNT)与表柔比星(EPI)联合用药对人肺腺癌GLC-82和A549细胞增殖和凋亡的影响。方法分别将GLC-82和A549细胞分为空白对照组、EPI组、LCNT组和EPI+LCNT组,给予对应药物作用24 h后采用噻唑蓝实验检测细胞增殖情况,流式细胞术检测细胞周期和早期凋亡情况,蛋白质印迹法检测P53和Bcl-2蛋白的表达。结果与空白对照组比,单独给药LCNT能促进GLC-82细胞的增殖,20.00 μg/ml LCNT作用24 h后GLC-82细胞的增殖率为37.56%(P<0.01),而A549细胞的增殖率仅为6.32%,差异无统计学意义(P>0.05)。EPI联合LCNT可减弱EPI对GLC-82细胞增殖的抑制作用,联合作用24 h后GLC-82细胞的增殖抑制率较EPI组降低了12.14%( P<0.05)。与EPI组相比,EPI联合LCNT可使GLC-82和A549细胞的G0/G1期比例明显升高[GLC-82:(50.42±1.21)%比(25.94±0.66)%,P<0.01;A549:(54.92±1.71)%比(38.63±0.69)%,P<0.01],GLC-82细胞的S期比例降低[(34.21±0.96)%比(59.68±1.25)%, P<0.05 ],并阻止GLC-82细胞早期凋亡,而不影响A549细胞的凋亡。与EPI组相比,EPI+LCNT组GLC-82和A549细胞中P53蛋白表达均下调(均P<0.05),但EPI+LCNT组GLC-82细胞中Bcl-2蛋白表达明显上调(P<0.01),而A549细胞中Bcl-2蛋白表达无明显变化(P>0.05)。结论 LCNT与EPI联用可减弱EPI对GLC-82细胞的增殖抑制作用和诱导凋亡作用,而对A549细胞无明显影响。LCNT能促进GLC-82细胞增殖,并使其细胞周期阻滞于G0/G1期,其机制可能与下调P53蛋白和上调Bcl-2蛋白的表达有关。Objective To investigate the effect of L-carnitine (LCNT) combined with epirubicin (EPI) on cell proliferation and apoptosis of two lung adenocarcinoma cell lines (GLC-82 and A549). Methods GLC-82 and A549 cells were divided into control group, EPI group, LCNT group and EPI+LCNT group, respectively. The cell proliferation rate was examined by MTT assay 24 h after the treatment, and the cell cycle and cell early apoptosis were analyzed by flow cytometry. The expression of P53 and Bcl-2 proteins were detected by Western Blot. Results Compared with the control group, the proliferation rate of GLC-82 and A549 cells was 37.56%(P<0.01) and 6.32%(P>0.05) after 24 hours of 20.00 μg/ml LCNT treatment indicating LCNT could promote the proliferation of GLC-82 cells. Compared with the EPI group, EPI+LCNT had smaller inhibitory effect on the proliferation of GLC-82 cells, and the inhibition rate of the EPI+LCNT group was 12.14% lower than that of EPI group (P<0.05). Compared with the EPI group, EPI+LCNT could significantly increase the G0/G1 phase ratio of GLC-82 cells (50.42%±1.21% vs. 25.94%±0.66%, P<0.01) and A549 cells (54.92%±1.71% vs. 38.63%±0.69%, P<0.01), decrease the S phase ratio of GLC-82 cells (34.21%±0.96% vs. 59.68%±1.25%, P<0.05), and prevent the early apoptosis of GLC-82 cells without affecting apoptosis of A549 cells. Moreover, in the EPI+LCNT group, the expression of P53 protein in GLC-82 and A549 cells was down-regulated (P<0.05), and the expression of Bcl-2 protein in GLC-82 cells was up-regulated (P<0.01) and no significant change in A549 cells (P>0.05). Conclusions Comparing with the EPI, the combination of LCNT and EPI has less proliferation inhibition and apoptosis induction on GLC-82 cells, and without significant effect on A549 cells. LCNT can promote the proliferation of GLC-82 cells and block the cell cycle at G0/G1 phase. This mechanism may be related to down-regulation of P53 protein and up-regulation of Bcl-2 protein expression.

关 键 词：肺肿瘤 腺癌 细胞增殖 细胞凋亡 左卡尼汀 表柔比星 

分 类 号：R734.2[医药卫生—肿瘤]