丙泊酚对奥沙利铂抗人胃癌BALB/c小鼠移植瘤作用的影响  

Effect of propofol on the anti-tumor effect of oxaliplatin in the transplanted tumor of human gastric cancer in BALB/c mice

作　　者：姜敬男 岳维[2] Jiang Jing-Nan;Yue Wei(College of Anesthesiology,Shanxi Medical University,Taiyuan 030000,China;Department of Anesthesiology,the Second Hospital of Shanxi Medical University,Taiyuan 030000,China)

机构地区：[1]山西医科大学麻醉学院,太原030000 [2]山西医科大学第二医院麻醉科,太原030000

出　　处：《解放军医学杂志》2021年第6期545-549,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金青年基金(34100940)。

摘　　要：目的探讨丙泊酚对奥沙利铂在人胃癌BALB/c小鼠移植瘤模型中抗肿瘤作用的影响。方法建立人胃癌MGC 803细胞BALB/c小鼠皮下移植瘤模型,随机分为对照组(n=6)、丙泊酚组(n=6,5 mg/kg丙泊酚)、奥沙利铂组(n=6,6 mg/kg奥沙利铂)与丙泊酚+奥沙利铂组(n=6,5 mg/kg丙泊酚+6 mg/kg奥沙利铂),每3d腹腔注射给药1次,连续3次。停药2 d后,采集血样并处死小鼠,取移植瘤称重,并测量移植瘤的长径和短径,计算小鼠移植瘤体积抑瘤率和质量抑瘤率。采用HE染色观察移植瘤细胞的形态学变化;ELISA法测定血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)以及移植瘤组织中表皮细胞生长因子(EGF)、基质金属蛋白酶-2(MMP-2)、MMP-9的表达水平。结果与对照组相比,丙泊酚组、奥沙利铂组及丙泊酚+奥沙利铂组移植瘤的体积(F=248.717,P<0.05)、质量(F=376.205,P<0.05)均有不同程度的降低。丙泊酚+奥沙利铂组移植瘤的体积抑瘤率、质量抑瘤率明显高于奥沙利铂组,差异有统计学意义(体积抑瘤率:82.44%±4.69%vs.47.18%±5.71%,P<0.05;质量抑瘤率:77.95%±3.64%vs.46.43%±3.99%,P<0.05)。HE染色显示,与对照组相比,丙泊酚组、奥沙利铂组及丙泊酚+奥沙利铂组移植瘤细胞的生长受到不同程度的抑制,癌细胞数量减少;其中丙泊酚+奥沙利铂组癌细胞数量减少最为明显,细胞核固缩为均一的蓝黑色致密物,胞质密度增大,核碎片增多,可见大面积坏死。ELISA检测结果显示,丙泊酚组、奥沙利铂组及丙泊酚+奥沙利铂组小鼠血清中TNF-α、IL-6以及移植瘤组织中EGF、MMP-2、MMP-9的表达水平均明显低于对照组,且丙泊酚+奥沙利铂组低于奥沙利铂组,差异有统计学意义(P<0.05)。结论丙泊酚可抑制胃癌细胞的增殖、侵袭和转移,并增高胃癌细胞对奥沙利铂的化疗敏感性,增强奥沙利铂的抗肿瘤作用,其机制可能与丙泊酚抑制炎症反应及调控EGF的表达有关。Objective To explore the effect of propofol on human gastric cancer transplant BALB/c mice model treated with oxaliplatin.Methods We established a human gastric cancer model in the BALB/c mice using MGC 803 cells subcutaneous transplantation.Then the mice were randomly divided into control group(n=6),propofol group(n=6,5 mg/kg propofol),oxaliplatin group(n=6,6 mg/kg oxaliplatin),and propofol with oxaliplatin group(n=6,5 mg/kg propofol+6 mg/kg oxaliplatin).The mice in each group received a total of 3 consecutive drug administrations through intraperitoneal injection once every 3 days.Mice were sacrificed two days after the last injection.Blood samples were then collected.The tumor volume and mass tumor inhibition rates were analyzed,respectively.The histological features of the tumor were evaluated with HE staining.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the serum were quantified using ELISA.In addition,the expression levels of epidermal growth factor(EGF),matrix metal protease-2(MMP-2)and MMP-9 proteins in transplanted tumor tissue were quantified using ELISA.Results Compared with control group,the volume tumor inhibition rates(F=248.717,P<0.05)and mass tumor inhibition rates(F=376.205,P<0.05)of propofol group,oxaliplatin group,and propofol+oxaliplatin group were significantly reduced.The tumor volume inhibition rate and mass tumor inhibition rate of propofol+oxaliplatin group were significantly lower than those of oxaliplatin group,and the differences were statistically significant(tumor volume inhibition rate:82.44%±4.69%vs.47.18%±5.71%,P<0.05;mass tumor inhibition rate:77.95%±3.64%vs.46.43%±3.99%,P<0.05).Compared with control group,cancer cell volume was reduced to varying degrees as well as the number of cancer cells was decreased in the remaining drug-treated groups using HE staining.In addition,the most significant decrease in cancer cell number happened in propofol+oxaliplatin group.The cell nucleus shrinks into a uniform blue-black dense body with an increase

关 键 词：丙泊酚 奥沙利铂 胃癌 移植瘤 

分 类 号：R730.51[医药卫生—肿瘤]