摘要
目的探讨罗哌卡因经原癌基因(c-MYC)信号通路抑制胃癌细胞增殖和迁移的机制。方法体外培养人胃癌MGC-803细胞进行实验,分为对照组、罗哌卡因低剂量组、罗哌卡因中剂量组、罗哌卡因高剂量组和顺铂组。罗哌卡因低、中、高剂量组分别给予终浓度为100、200、400μg/mL的罗哌卡因;顺铂组给予终浓度为10 mmol/mL的顺铂;对照组无处理。继续培养24 h后,细胞计数试剂盒8(CCK-8)法检测细胞增殖率,细胞划痕法检测MGC-803细胞迁移能力,同时检测MGC-803细胞中蛋白激酶C(PKC)、c-MYC、金属蛋白酶-9(MMP-9)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)和哺乳动物雷帕霉素靶蛋白(mTOR)蛋白表达。结果罗哌卡因低、中、高剂量组和顺铂组的MGC-803细胞增殖率[(92.05±8.24)%、(76.26±6.93)%、(53.18±5.86)%、(42.18±15.17)%]和迁移能力[(36.34±4.03)μm、(31.21±3.56)μm、(24.60±2.57)μm、(18.07±1.26)μm]较对照组[(100.00±5.91)%、(40.12±5.17)μm]明显降低(P<0.05);上述各组MGC-803细胞中PKC[(0.62±0.06)、(0.50±0.08)、(0.42±0.08)、(0.36±0.10)]、c-MYC[(0.53±0.09)、(0.49±0.15)、(0.43±0.02)、(0.31±0.04)]、MMP-9[(0.47±0.03)、(0.42±0.05)、(0.30±0.04)、(0.21±0.06)]、PI3K[(0.39±0.04)、(0.33±0.08)、(0.28±0.04)、(0.25±0.01)]、AKT[(0.50±0.10)、(0.43±0.09)、(0.24±0.02)、(0.16±0.03)]和mTOR[(0.42±0.05)、(0.36±0.03)、(0.30±0.02)、(0.25±0.04)]表达较对照组[(0.74±0.08)、(0.63±0.06)、(0.53±0.05)、(0.46±0.07)、(0.71±0.04)、(0.49±0.06)]明显降低(P<0.05),且各罗哌卡因剂量组降低强度呈剂量依赖性,但各指标均仍高于顺铂组(P<0.05)。结论罗哌卡因可抑制人胃癌MGC-803细胞增殖和迁移,其机制可能与抑制c-MYC信号通路的激活有关。
Objective To investigate the mechanism of ropivacaine inhibiting the proliferation and migration of gastric cancer cells via Proto-oncogene(c-MYC)signaling pathway.Methods MGC-803 cells of human gastric cancer were cultured in vitro,and the control group was not treated.The final concentration of ropivacaine was 100,200,400μg/mL in the low-dose ropivacaine group,the middle dose ropivacaine group and the high-dose ropivacaine group respectively.The final concentration of cisplatin was 10 mmol/mL in the cisplatin group.After continuous culture for 24 hours,the cell proliferation rate was detected by Cell count kit 8(CCK-8)method,the migration ability of MGC-803 cells was detected by cell scratch method,and the expressions of Protein kinase C(PKC),c-MYC,Matrix metalloproteinase-9(MMP-9),Phosphatidylinositol 3 kinase(PI3K),Protein kinase B(Akt)and mammalian Target of rapamycin(mTOR)protein in MGC-803 cells were detected.Results The proliferation rate of MGC-803 cells in each ropivacaine dose group and cisplatin group[(92.05±8.24)%,(76.26±6.93)%,(53.18±5.86)%,(42.18±15.17)%]and migration ability[(36.34±4.03)μm,(31.21±3.56)μm,(24.60±2.57)μm,(18.07±1.26)μm]were significantly lower than those in the control group[(100.00±5.91)%,(40.12±5.17)μm](P<0.05).The expressions of PKC[(0.62±0.06),(0.50±0.08),(0.42±0.08),(0.36±0.10)],c-MYC[(0.53±0.09),(0.49±0.15),(0.43±0.02),(0.31±0.04)],MMP-9[(0.47±0.03),(0.42±0.05),(0.30±0.04),(0.21±0.06)],PI3K[(0.39±0.04),(0.33±0.08),(0.28±0.04),(0.25±0.01],AKT[(0.50±0.10),(0.43±0.09),(0.24±0.02),(0.16±0.03)]and mTOR[(0.42±0.05),(0.36±0.03),(0.30±0.02),(0.25±0.04)]in MGC-803 cells were significantly lower than those in the control group[(0.74±0.08),(0.63±0.06),(0.53±0.05),(0.46±0.07),(0.71±0.04),(0.49±0.06)](P<0.05),and the reduction intensity of each ropivacaine dose group was dose-dependent,but the levels of each indicators were still higher than those in the cisplatin group(P<0.05).Conclusion Ropivacaine can inhibit the proliferation and migration
作者
洪勇
周民伟
徐化交
HONG Yong;ZHOU Min-wei;XU Hua-jiao(Department of Anesthesiology,the 922th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Hengyang 421002,Hunan,China)
出处
《东南国防医药》
2020年第5期456-460,共5页
Military Medical Journal of Southeast China
关键词
罗哌卡因
c-MYC信号通路
胃癌
细胞增殖
细胞迁移
ropivacaine
c-MYC signaling pathway
gastric cancer
cell proliferation
cell migration
