美洛昔康不诱导胃癌细胞耐药

No induction of drug-resistance by meloxicam on human gastric carcinoma cell SGC7901

目的旨在了解环氧合酶-2(cyc looxygenase-2,COX-2)抑制剂美洛昔康对胃癌细胞的长期作用能否导致胃癌细胞对其产生耐药性。方法采用浓度递增法结合大剂量冲击法,美洛昔康长期作用于胃癌SGC7901细胞,时间达6个月,尝试诱导胃癌美洛昔康耐药株,命名为SGC7901/M,并用MTT法测定药物敏感性,光镜、电镜观察细胞形态学改变,活细胞计数法和克隆形成技术了解其生物学特性。结果药物敏感分析显示,胃癌细胞经过美洛昔康长期作用,对美洛昔康并没有出现抗性,其IC50与亲代细胞比较差异无统计学意义(P>0.05),分别为4.6×10-4±2.23×10-4mol.L-1,3.54×10-4±2.34×10-4mol.L-1。SGC7901/M细胞对美洛昔康的耐药指数约为1.3。SGC7901/M细胞与亲代细胞形态学比较,光镜及电镜均未显示差异,两种细胞在经1×10-3mol.L-1美洛昔康作用24 h后,均表现出细胞受到明显损伤和凋亡的形态。无论从生长曲线上还是克隆形成率上都显示SGC7901/M细胞与亲代细胞的生长特性无差异。结论美洛昔康可抑制胃癌细胞生长,长期用药不诱导胃癌细胞产生耐药性。

Aim This study aimed to investigate whether a long-time exposure of gastric carcinoma cells to meloxicam, a COX-2 inhibitor, would result in drug-resistance to it. Methods In order to establish a meloxicam-resistant human gastric cancer cell line, gastric cancer cells were continuously exposed to gradually increasing concentrations of meloxicam and later intermittently exposed to high-dose of meloxicam for 6 months. The established cell line was named SGC7901/M. The growth abilities of SGC7901/M were determined using cell counting, colony formation technique and MTT method. By using light microscope and electron microscope, the morphologic alterations of cells were observed. Results Drug sensitivity assay showed that gastric cancer cells were not resistant to meloxicam after a long-time exposure to it. The IC50 of induced cells and parental cells was not markedly different, being （4.6 × 10^-4 ± 2.23 × 10^-4 ） mol · L^-1 and （3.54 × 10^-4 ±2.34 × 10^-4） mol · L^-1 , respectively （ P 〉 0. 05 ）. The resistance index （RI） of SGC7901/M cells to meloxicam was about 1.3 fold. Under light microscope or electron microscope, no morphological differences between SGC7901/M and parental cells were observed. While the two cell lines were treated with 1 × 10^-3 mol · L^-1 meloxicam for 24 h they both exhibited signs of cell damage and apoptosis. Both growth curves and colony formation efficiency showed that there was no marked difference in the proliferations between SGC7901/M and parental cells. Conclusion After a long-time exposure to meloxicam, gastric cancer cells maintain the sensitivity to the drug, and no development of resistance to meloxicam is observed.