TRAIL对人胃癌耐药细胞株SGC-7901/VCR多药耐药基因GST-π表达的影响

王慧群*张开光#王俊先王巧民

安徽省立医院消化内科(230001)

背景：肿瘤细胞的多药耐药现象是导致进展期胃癌化疗失败的重要因素之一。肿瘤坏死因子相关凋亡诱导配体(TRAIL)能增强化疗药物对肿瘤细胞的杀伤作用，并逆转耐药细胞株为敏感细胞株，但其确切机制尚不清楚。目的：研究TRAIL对人胃癌耐药细胞株SGC-7901/VCR多药耐药基因谷胱甘肽硫转移酶-π(GST-π)表达的影响，探讨其逆转胃癌细胞多药耐药的可能机制。方法：以不同浓度TRAIL(50、100、200、400 μg/L)干预SGC-7901/VCR细胞48 h，采用RT-PCR和ELISA法检测各组SGC-7901/VCR细胞中的GST-π mRNA表达和细胞培养上清液中的GST-π含量。结果：TRAIL干预能抑制SGC7901/VCR细胞的GST-π mRNA表达及其蛋白分泌，抑制作用在一定剂量范围内(≤200 μg/L)具有量效关系。50、100、200、400 μg/L TRAIL组GST-π mRNA相对表达量分别为0.89±0.04、0.77±0.08、0.65±0.06和0.61±0.03，细胞培养上清液中的GST-π含量分别为(57.56±1.19) ng/mL、(56.30±0.80) ng/mL、(31.41±1.65) ng/mL和(30.80±1.34) ng/mL，均低于对照组的1.01±0.13和(58.62±1.38) ng/mL，差异有统计学意义(P<0.05)。结论：TRAIL可能通过下调GST-π表达参与了胃癌细胞多药耐药的逆转。

关键词胃肿瘤；TNF相关凋亡诱导配体；谷胱甘肽转移酶；多药耐药

Effect of TRAIL on Expression of Multidrug Resistance Gene GST-π in Drug-resistant Human Gastric Cancer Cell Line SGC7901/VCRWANGHuiqun,ZHANGKaiguang,WANGJunxian,WANGQiaomin.DepartmentofGastroenterology,AnhuiProvincialHospital,Hefei(230001)

Correspondence to: ZHANG Kaiguang, Email: zhangkaiguang@medmail.com.cn

Background: Multidrug resistance of tumor cells is one of the important factors that cause failure of chemotherapy in advanced gastric cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may enhance the killing effect of chemotherapeutics on tumor cells, and reverse drug-resistant cell lines to sensitive cell lines, but its mechanism is not yet clear. Aims: To study the effect of TRAIL on expression of multidrug resistance gene glutathione S-transferase-π (GST-π) in drug-resistant human gastric cancer cell line SGC-7901/VCR and the potential mechanism of TRAIL in reversing multidrug resistance of gastric cancer cells. Methods: SGC-7901/VCR cells were treated with TRAIL in different doses (50, 100, 200 and 400 μg/L) for 48 hours. After treatment, expression of GST-π mRNA in SGC-7901/VCR cells and concentration of GST-π in culture supernatant were detected by RT-PCR and ELISA, respectively. Results: TRAIL could inhibit mRNA expression and protein secretion of GST-π in SGC-7901/VCR cells in a dose-dependent manner within a certain range (≤200 μg/L). The relative expression levels of GST-π mRNA in 50, 100, 200 and 400 μg/L TRAIL groups were 0.89±0.04, 0.77±0.08, 0.65±0.06 and 0.61±0.03, respectively, and the concentrations of GST-π in culture supernatant in these groups were (57.56±1.19) ng/mL, (56.30±0.80) ng/mL, (31.41±1.65) ng/mL and (30.80±1.34) ng/mL, respectively, all were significantly lower than those in control group [1.01±0.13 and (58.62±1.38) ng/mL,Pall <0.05]. Conclusions: TRAIL may play a potential role in reversing multidrug resistance of gastric cancer cells through down-regulating GST-π expression.

Key wordsStomach Neoplasms;TNF-Related Apoptosis-Inducing Ligand;Glutathione Transferase;Multidrug Resistance

胃癌是消化系统最常见的恶性肿瘤[1]，化疗是胃癌尤其是进展期胃癌的重要治疗手段，而肿瘤细胞的多药耐药(multidrug resistance)现象是导致胃癌化疗失败的重要因素之一。因此，研究多药耐药的发生机制及其影响因素对寻求逆转多药耐药的对策具有重要意义。肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand, TRAIL)能增强化疗药物对肿瘤细胞的杀伤作用，并逆转耐药细胞株为敏感细胞株[2-3]，但其确切机制尚不清楚。有研究[4-6]发现抑制肿瘤细胞多药耐药基因表达可有效逆转多药耐药，增加对化疗药物的敏感性，由此推测TRAIL亦可能通过影响多药耐药基因表达而发挥化疗增敏作用。……