塞来昔布增强胃癌化疗药物疗效的机制研究

Study on the mechanism of celecoxib on synergetic anti-tumor role in gastric cancer in vitro

目的研究塞来昔布(特异性环氧合酶-2抑制剂)增强胃癌化疗药疗效的分子机制。方法以3个浓度(10、50、150mmol.L-1)塞来昔布干预胃癌细胞BGC-823株48h,用RT-PCR法观察用药前后多药耐药(MDR)相关基因如MDR1、多药耐药相关蛋白(MRP)和谷光甘肽-S-转移酶π(GST-π)基因的表达变化。结果胃癌细胞BGC-823株存在内在多药耐药性,表现为有MRP和GST-π表达、无MDR1表达。塞来昔布干预后,MRP和GST-π均有不同程度下降(P<0.05或P<0.01)。结论塞来昔布可通过抑制MDR相关基因如MRP和GST-π起化疗增敏剂作用。

Objective To investigate the conceivable molecular mechanism of a specific eyelooxygenase - 2 inhibitor eeleeoxib on synergetie anti - tumor role in gastric cancer in vitro. Methods Gastric cell line BGC -823 was interfered by a specific eyelooxygenase inhibitor celeeoxib, 10,50 and 150 mmol · L^-1, respectively. The expression and changes of multidrug resistance （MDR） gene family was assessed by reverse transcription - polymerase chain reaction. Results MDR gene family was detected on gastric cancer cell line BGC -823, the positive expression were multidrug - associated protein （MRP） and glutathione - S - trans- ferases -π （GST -π） gene, but MDR1 gene was undeteetable. After treatment with eeleeoxib （concentration range of 10 - 150 mmol·L^-1 ）, a significant down regulation of MRP and GST -π mRNA was observed （ P 〈 0.05 or P 〈 0.01 ）. Conclusion By inhibiting the intrinsic multidrug resistance, eeleeoxib plays a synergetie anti -tumor role in chemotherapy drugs on gastric cancer cell line BGC -823.