| 摘要: |
| 目的观察榄香烯对人胃癌SGC-7901细胞株体外和体内增殖、抑制及凋亡的作用，并探讨其可能的作用机制。方法采用不同药物对培养后的人胃癌SGC-7901细胞株进行处理并分为4组：对照组、榄香烯组、细胞外信号调控的蛋白激酶1/2（ERK1/2）信号通路抑制剂PD98059组和榄香烯+PD98059联合组；再将20只雄性裸鼠随机分为4组：甲组（腹腔注射0.9%氯化钠注射液）、乙组（腹腔注射榄香烯最大耐受剂量200mg/kg）、丙组（腹腔注射PD98059最大耐受剂量1mg/kg）、丁组（腹腔注射最大耐受剂量榄香烯+PD98059），均制作胃癌移植瘤模型，并腹腔注射不同药物进行治疗。观察榄香烯和PD98059对细胞株相关蛋白的表达情况及裸鼠胃癌移植瘤的大小及对裸鼠生长的影响。采用MTT法检测细胞增殖情况，Western-blot法检测ERK1/2、磷酸化细胞外信号调控的蛋白激酶1/2（p-ERK1/2）、p38丝裂原活化蛋白激酶（p38）、磷酸化p38丝裂原活化蛋白激酶（p-p38）的表达，real-timeRT-PCR检测Bcl-2mRNA及BaxmRNA的表达，TUNEL法检测胃癌细胞凋亡并计算凋亡指数。结果与对照组相比，榄香烯组随药物浓度的增加，p-ERK1/2表达增加（P＜0.05或0.01），BaxmRNA的表达增加（均P＜0.01），Bcl-2mRNA的表达降低[除榄香烯0.02mg/ml外，其他浓度均具有统计学差异（均P＜0.01）]，而总ERK1/2的表达无明显变化（均P＞0.05）；榄香烯、PD98059及榄香烯+PD98059对胃癌细胞增殖均具有抑制作用（均P＜0.05），且两药联合的抑制作用最好；榄香烯、PD98059及榄香烯+PD98059组细胞凋亡率均高于对照组（P＜0.05或0.01），并具有浓度依赖性，且两药联合组的凋亡率明显高于单一用药组（均P＜0.05）；乙、丁两组移植瘤的瘤重均较甲组明显减小（P＜0.05或0.01），且两药联合时抑瘤率达75.59%。结论榄香烯对肿瘤细胞具有抑制作用，且可能是通过上调p-ERK1/2和p-p38蛋白的表达促进胃癌细胞和移植瘤的凋亡，另榄香烯与PD98059联合使用时对肿瘤细胞及组织具有协同抑制效应。 |
| 关键词: 胃癌 榄香烯 PD98059 细胞凋亡 移植瘤 |
| DOI： |
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| 基金项目:浙江省医药卫生科技计划项目 |
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| Inhibitory effects of elemene on proliferation of human gastric cancer SGC-7901 cells and its mechanism |
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TU Yangyang, YU Yaohui, LIN Haihong, LI Peihong, YE Sunzhi, SUN Weijian, YAO Zhichao, ZHENG Zhiqiang
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the Second Affiliated Hospital of Wenzhou Medical University
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| Abstract: |
| Objective To investigate the effects of elemene on the proliferation and apoptosis of human gastric cancer SGC-7901 cells and its mechanism. Methods Treat to SGC-7901 gastric cancer cells with different drugs dividing into four groups : control group, elemene group, extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathway inhibitor PD98059 group, elemene joint PD98059 group and then twenty male nude mice were inoculated with human gastric cancer SGC-7901 Cells and randomly divided in to 4 groups equally. The tumor-bearing mice were injected peritoneally with 0.9% saline (group A, control), elemene (200mg/kg, group B), ERK1/2 inhibitor PD98059(1mg/kg, group C) or elemene and PD98059 (group D), respectively. The tumor size was measured. The cultured SGC-7901 cells were treated with different concentration of elemene in vitro. Cell proliferation was determined with MTT method. The expression of extracellular signal-regulated kinase1/2 (ERK1/2), phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2), p38 mitogen-activated protein kinase (p38) and phosphorylated p38 mitogen-activated protein kinase (p-p38) was detected with Western blot; the expression of Bcl -2 mRNA and Bax mRNA was detected with real-time RT-PCR and cell apoptosis was detected with TUNEL method and the apoptosis index was calculated. Results With increasing concentration of elemene, expression of p-ERK1/2 protein and Bax mRNA
increased (P ＜0.05 or 0.01); while the expression of Bcl-2 mRNA reduced and the total ERK1/2 had no significant changes.
Elemene group, PD98059 group and elemene joint PD98059 group all have inhibitory effect on gastric cancer cell proliferation rate (all P＜0.05), and inhibition effect of the joint of the two drugs is best . Apoptosis rate of the cells of elemene group、PD98059 group and elemene joint PD98059 group are all higher than control group (P＜0.05 or 0.01) and have concentration dependence, and apoptosis rate of the elemene joint PD98059 group is obviously higher than that of single group (all P＜0.05). The weight of transplantation tumor in group B and D nude mice are less than A group (P＜0.05 or 0.01), and the joint inhibitory rate is 75.59% when the two drugs joint. Conclusion Elemene can inhibit growth and promote apoptosis of gastric cancer cells in vitro and in vi- vo, in which p-ERK1/2 and p-p38 signaling pathways maybe involved. In addition, the combination of elemene with PD98059 may
have synergistic inhibition effect on gastric cancer cells. |
| Key words: Gastric cancer Elemene PD98059 Cell apoptosis Transplantation tumor |
