Wu Quan, Yu Jian-chun, Liu Yu-qin, Kang Wei-ming, Guo Wei-dong
Department of General Surgery, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010 Feb;32(1):65-70. doi: 10.3881/j.issn.1000-503X.2010.01.016.
To evaluate the effect of the combination of docosahexaenoic acid (DHA) and fluorouracil (FU) on human gastric carcinoma cell strain MGC803 in vitro.
The influences of DHA and FU alone or in combination on cell proliferation was detected using MTT assay. Dose of median (Dm) of drugs (alone or in combination) and the combination index (CI) were calculated using the combination index equation of Chou-Talalay. Cell cycle were examined using flow cytometry. Cell apoptosis was determined by Annexin V-FITC/PI double staining method. The expression of apoptosis-related protein was detected using Western blot.
DHA significantly inhibited the growth of MGC803, and low-dose DHA induced the proliferation of human embryonic lung fibroblast (P < 0.05). DHA remarkably strengthened the inhibitive effect of FU on the growth of MGC803, and decreased the Dm of FU by 3.6-2.5 folds (P < 0.05). When the inhibitory ratio reached 30%, the combination of DHA and FU showed synergism (CI < 1) and significant G(0)/G(1) arrest (vs FU, P < 0.05). DHA increased the apoptosis-inducing effect of FU and upregulated the cleaved-caspase-3 expression.
DHA can inhibit the growth of MGC803. When combined with FU, DHA has synergetic effect in inhibiting the proliferation of gastric cancer cells and meanwhile decrease the dose of FU.
评估二十二碳六烯酸（DHA）与氟尿嘧啶（FU）联合应用对人胃癌细胞株MGC803的体外作用。
采用MTT法检测DHA和FU单独及联合应用对细胞增殖的影响。使用Chou-Talalay联合指数方程计算药物（单独或联合）的半数效应剂量（Dm）和联合指数（CI）。采用流式细胞术检测细胞周期。通过Annexin V-FITC/PI双染法测定细胞凋亡。采用蛋白质免疫印迹法检测凋亡相关蛋白的表达。
DHA显著抑制MGC803的生长，低剂量DHA促进人胚肺成纤维细胞增殖（P<0.05）。DHA显著增强FU对MGC803生长的抑制作用，使FU的Dm降低3.6至2.5倍（P<0.05）。当抑制率达到30%时，DHA与FU联合显示协同作用（CI<1），并导致显著的G(0)/G(1)期阻滞（与FU相比，P<0.05）。DHA增强了FU的诱导凋亡作用，并上调了裂解的caspase-3表达。
DHA可抑制MGC803的生长。与FU联合应用时，DHA在抑制胃癌细胞增殖方面具有协同作用，同时可降低FU的剂量。
