Zhu Zhi-xia, Zhang Wei-min, Jia Gang, Zhou Juan
Department of Oncology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2010 Jan;30(1):149-52.
To investigate the sequence-dependent effect of combined use of gemcitabine and pemetrexed on the proliferation of human pancreatic carcinoma cell lines BXPC-3 and PANC-1 in vitro and explore the cellular mechanism.
MTT assay was used to determine the proliferation of the two cells after addition of the two drugs in different sequences, and the cell cycle changes were analyzed by flow cytometry.
Both gemcitabine (10(-7)-10 mg/ml) and pemetrexed (10(-7)-10 mg/ml) significantly inhibited the proliferation of BXPC-3 and PANC-1 cells in a dose- and time-dependent manner. The effect of combined administration of gemcitabine and pemetrexed on the cell proliferation varied with the order of the drug delivery, and addition of gemcitabine 24 h after pemetrexed administration produced a significant enhancement of the inhibitory effect as compared with simultaneous drug administration (P<0.05) or the administration of the two drugs in a reverse order (P<0.05). Compared with the control group, combined administration of gemcitabine and pemetrexed caused obvious cell cycle arrest at G1 and S phases (P<0.05). Simultaneous administration of the two drugs resulted in significantly reduced G2-phase cells (P<0.05); addition of gemcitabine prior to pemetrexed caused cell cycle arrest in G1 phase (P<0.05), while the reverse caused cell cycle in S phase (P<0.05).
Both gemcitabine and pemetrexed can inhibit the proliferation of BXPC-3 and PANC-1 cells, and their synergetic effect depends on the sequence of their administration. The sequential administration of pemetrexed followed by gemcitabine produces significant synergetic effects against the cell proliferation, which might not be associated with their influence of the cell cycle.
研究吉西他滨与培美曲塞联合使用对人胰腺癌细胞系BXPC - 3和PANC - 1体外增殖的序列依赖性影响，并探讨其细胞机制。
采用MTT法检测两种药物以不同顺序添加后两种细胞的增殖情况，通过流式细胞术分析细胞周期变化。
吉西他滨（10⁻⁷ - 10 mg/ml）和培美曲塞（10⁻⁷ - 10 mg/ml）均以剂量和时间依赖性方式显著抑制BXPC - 3和PANC - 1细胞的增殖。吉西他滨与培美曲塞联合给药对细胞增殖的影响随给药顺序而异，培美曲塞给药24小时后添加吉西他滨与同时给药相比，抑制作用显著增强（P<0.05），与两种药物以相反顺序给药相比也显著增强（P<0.05）。与对照组相比，吉西他滨与培美曲塞联合给药导致明显的细胞周期阻滞在G1期和S期（P<0.05）。两种药物同时给药导致G2期细胞显著减少（P<0.05）；培美曲塞之前添加吉西他滨导致细胞周期阻滞在G1期（P<0.05），而相反顺序则导致细胞周期在S期（P<0.05）。
吉西他滨和培美曲塞均可抑制BXPC - 3和PANC - 1细胞的增殖，它们的协同作用取决于给药顺序。培美曲塞后序贯给予吉西他滨对细胞增殖产生显著的协同作用，这可能与其对细胞周期的影响无关。
