Strouch Matthew J, Milam Benjamin M, Melstrom Laleh G, McGill John J, Salabat Mohammad R, Ujiki Michael B, Ding Xian-Zhong, Bentrem David J
Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Pancreas. 2009 May;38(4):409-15. doi: 10.1097/MPA.0b013e318193a074.
The aim of the study was to evaluate the effect of combination therapy of apigenin and gemcitabine on cell proliferation, the cell cycle, and gemcitabine resistance in human pancreatic cancer cells.
Cell counting was used to assess the effect of single-agent and combination treatment on the proliferation of CD18 and AsPC-1 pancreatic cancer cells. Flow cytometry was performed to assess the effect of combination treatment on cell cycle progression and induction of apoptosis. Western blot analysis was used to evaluate phosporylated AKT (pAkt) and cell cycle proteins. The effect of apigenin on gemcitabine-resistant AsPC-1 cells was assessed via thymidine incorporation.
Apigenin in combination with gemcitabine inhibited pancreatic cancer cell proliferation more than either agent alone. Combination treatment induced both S and G2/M phase arrest and increased apoptosis. Apigenin down-regulated pAkt expression and abrogated gemcitabine-mediated pAkt induction. In gemcitabine-resistant AsPC-1 cells, apigenin significantly inhibited cell proliferation in a dose-dependent manner.
Combination treatment with apigenin and gemcitabine inhibited pancreatic cancer cell growth via cell cycle arrest, down-regulation of the prosurvival factor pAkt, and induction of apoptosis. Combination therapy may prove useful for the treatment of pancreatic cancer.
本研究旨在评估芹菜素与吉西他滨联合治疗对人胰腺癌细胞增殖、细胞周期及吉西他滨耐药性的影响。
采用细胞计数法评估单药及联合治疗对CD18和AsPC-1胰腺癌细胞增殖的影响。通过流式细胞术评估联合治疗对细胞周期进程及凋亡诱导的影响。采用蛋白质免疫印迹分析评估磷酸化AKT（pAkt）和细胞周期蛋白。通过胸腺嘧啶核苷掺入法评估芹菜素对吉西他滨耐药的AsPC-1细胞的影响。
芹菜素与吉西他滨联合使用比单独使用任一药物更能抑制胰腺癌细胞增殖。联合治疗诱导S期和G2/M期阻滞并增加凋亡。芹菜素下调pAkt表达并消除吉西他滨介导的pAkt诱导。在吉西他滨耐药的AsPC-1细胞中，芹菜素以剂量依赖方式显著抑制细胞增殖。
芹菜素与吉西他滨联合治疗通过细胞周期阻滞、下调促生存因子pAkt及诱导凋亡来抑制胰腺癌细胞生长。联合治疗可能对胰腺癌治疗有用。
