维生素B2在胃癌中的作用及机制研究

The role and mechanism of vitamin B2 in gastric cancer

目的探讨维生素B2(Vit B2)在胃癌中的表达及其生物学意义。方法选择39例胃癌患者(胃癌组)和40例健康体检者(对照组),检测2组血清Vit B2水平,分析其与胃癌患者临床病理特征的关系。培养人胃癌MGC-803细胞,并取对数生长期细胞分别给予0、10、25、50、100μmol/L Vit B2处理,检测细胞氧化磷酸化(葡萄糖、乳酸和琥珀酸脱氢酶)水平。实时荧光定量PCR(qPCR)检测己糖激酶Ⅱ(HKⅡ)、丙酮酸激酶M2(PKM2)和葡萄糖转运体1(GLUT1)mRNA水平。CCK-8法检测胃癌MGC-803细胞的增殖活性。流式细胞术检测胃癌细胞的凋亡情况。结果胃癌患者血清Vit B2水平低于对照组[(207.85±39.71)μg/L vs.(246.07±45.43)μg/L],且血清Vit B2水平与胃癌患者的TNM分期和分化程度有关;与0μmol/L Vit B2组相比,25、50、100μmol/L Vit B2组细胞葡萄糖消耗量和乳酸生成量均降低,琥珀酸脱氢酶含量均升高,HKⅡ、PKM2和GLUT1 mRNA水平均降低(均P<0.05);且50μmol/L Vit B2组变化最明显。对照组、Vit B2组、阿帕替尼组和联合用药组胃癌细胞增殖活性依次降低,细胞凋亡率依次升高,组间多重比较差异均有统计学意义(P<0.05)。结论胃癌患者血清Vit B2水平降低,Vit B2和阿帕替尼联合用药可提高其对胃癌的抗肿瘤效果。

Objective To investigate the expression and biological effects of vitamin B2 in gastric cancer.Methods Thirty-nine patients with gastric carcinoma(gastric cancer group)and 40 healthy controls(control group)were collected in this study.The serum expressions of vitamin B2 were detected in the two groups.The relationship between the level of vitamin B2 and the clinical pathological characteristics of gastric cancer patients was analyzed.Human gastric cancer MGC-803 cells were cultured and treated with 0μmol/L,10μmol/L,25μmol/L,50μmol/L and 100μmol/L vitamin B2 respectively.Glucose,lactic acid and succinate dehydrogenase levels were detected by biochemical kit.The mRNA expressions of HKⅡ,PKM2 and GLUT1 were detected by qPCR.The cell proliferation was detected by CCK-8.Moreover,the cell apoptosis was detected by flow cytometry.Results Compared with control group,the serum expression of vitamin B2 was significantly decreased in gastric cancer group(207.85μg/L±39.71μg/L vs.246.07μg/L±45.43μg/L,P<0.05).The serum expression of vitamin B2 was related with tumor TNM staging and the differentiation degree in patients with gastric cancer(P<0.05).Compared with 0μmol/L group,glucose consumption and lactate production were significantly decreased,while the content of succinate dehydrogenase was increased in 25μmol/L,50μmol/L and 100μmol/L groups(P<0.05).Compared with 0μmol/L group,HKⅡ,PKM2 and GLUT1 mRNA expressions were significantly decreased in 25μmol/L,50μmol/L and 100μmol/L groups(P<0.05).Compared with the control group,the cell proliferation activities were decreased in turn in vitamin B2,Apatinib and combination groups(P<0.05).Moreover,the combination could further reduce the cell proliferation activity(P<0.05).Compared with the control group,the cell apoptosis rates were increased in turn in vitamin B2,Apatinib and combination groups(P<0.05).Conclusion The serum vitamin B2 levels decrease in patients with gastric cancer.The combination of vitamin B2 and apatinib could improve the anti-tumor effect on gastric cancer.