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高血糖环境对胃癌组织及胃癌细胞 P- 糖蛋白和拓扑异构酶 2α 表达的影响
陈锐1, 王展, 黄寿奖, 赵伟2
1.浙江大学医学院附属儿童医院新生儿外科;2.西安交通大学第一附属医院胃肠外科
摘要:
目的 探讨高血糖环境对胃癌组织及体外培养的胃癌细胞中的 P- 糖蛋白(P-gp)和拓扑异构酶 2α(Top-Ⅱ α)表达的影响。 方法 采用免疫组化检测 40 例胃癌患者和 30 例 2 型糖尿病(T2DM)合并胃癌患者癌组织中的 P-gp 和 Top-Ⅱ α 的表达情况;体外培养人胃癌细胞株 SGC7901,给予不同浓度的葡萄糖干预,Western blot 检测各组细胞中的 P-gp 和 Top-Ⅱα 蛋白表达;MTT 法检测各组细胞对 5- 氟尿嘧啶(5-Fu)的敏感性变化。 结果 40 例胃癌患者癌组织中的 P-gp 的平均阳性光密度 值为 0.0146±0.0173,30 例 T2DM 合并胃癌患者癌组织中 P-gp 的平均阳性光密度值为 0.0215±0.0095,两组间比较有统计学差异 (P<0.01)。40 例胃癌患者癌组织中的 Top-Ⅱα的平均阳性光密度值为 0.0233±0.0158,30 例 T2DM 合并胃癌患者癌组织中的 Top-Ⅱα的平均阳性光密度值为 0.0229±0.0101,两组间比较无统计学差异(P >0.05)。Western blot 结果显示高浓度葡萄糖组 P-gp 的蛋白相对表达量为 2.920±0.091,中浓度葡萄糖组为 2.530±0.094,正常浓度葡萄糖组为 1.560±0.088,组间比较有统计学 差异(P<0.01);高浓度葡萄糖组 Top-Ⅱα 的蛋白相对表达量为 0.180±0.026,中浓度葡萄糖组为 0.830±0.073,正常浓度葡萄糖组 为 0.580±0.039,组间比较有统计学差异(P<0.01)。MTT 结果显示高浓度葡萄糖环境下胃癌细胞对 5-Fu 的敏感性下降。 结论 高 血糖环境下胃癌组织和体外培养的胃癌细胞表达 P-gp 蛋白量增加且对化疗药物 5-Fu 的敏感性下降。
关键词:  胃癌 2 型糖尿病 P- 糖蛋白 拓扑异构酶 2α 高血糖
DOI:
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基金项目:浙江省教育厅科研项目
Effect of exposure to high glucose on expression of p-glycoprotein and topoisomerase Ⅱ 琢 in gastric cancer tissues and cell line
CHEN Rui,WANG Zhan,HUANG Shoujiang,ZHAO Wei
the Children Hospital Zhejiang University School of Medicine
Abstract:
Objective To investigate the effect of exposure to high glucose on the expression of p-glycoprotein (P-gp) and topoisomerase Ⅱα(Top-Ⅱα) protein in gastric cancer tissue and cell line. Methods The expression of p-glycoprotein and topoisomerase Ⅱα protein in tissue samples from 40 patients with gastric cancer and 30 patients with gastric cancer and type 2 diabetes mellitus (T2DM) was detected by immunohistochemistry. The cultured human gastric cancer SGC7901 cells were exposed to different concentrations of glucose. The levels of p-glycoprotein and topoisomerase Ⅱα protein were determined by Western blot. The cell viability was examined with MTT method after SGC7901 cells were treated with 5-Fu under high glucose. Results The optical density of P-gp in gastric cancer tissue and gastric cancer with T2DM was 0.0146±0.0173 and 0.0215±0.0095(P<0.01). The optical density of Top-Ⅱα in gastric cancer tissue and gastric cancer with T2DM tissue was 0.0233±0.0158 and 0.0229 ±0.0101(P >0.05). Western blot showed that the relative expression of P-gp in high, middle and normal glucose groups was 2.920±0.091, 2.530±0.094; and 1.560±0.088, respectively (P<0.01); the relative expression of Top-Ⅱα protein in high, middle and normal glucose groups was 0.180±0.026, 0.830±0.073 and 0.580±0.039, respectively(P<0.01). MTT results showed that the sensitivity of SGC7901 cells to 5-FU was inhibited in high glucose group. Conclusion The expression of P-gp protein in gastric cancer tissues and cell line is increased under high glucose exposure, which may be associated with the resistance to chemotherapy drugs.
Key words:  Gastric cancer T2DM P-glycoprotein Topoisomerase Ⅱα Hyperglycaemia