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目的:研究环氧化酶-2 (COX -2)抑制剂塞来昔布联合阿霉素对胃癌MGC -803细胞株的凋亡诱导作用,并探讨其相互作用的可能的分子机制。方法:用MTT法检测MGC -803的增殖情况。用荧光显微镜、流式细胞术和DNA梯度电泳检测肿瘤细胞凋亡的情况。结果:随着阿霉素剂量的增加,MGC -803细胞的数量明显减少。细胞大部分静止于G0/G1期,S期细胞明显减少。阿霉素(5 mg/L)联合塞来昔布(25μmol/L)明显抑制MGC -803细胞的生长。肿瘤细胞经阿霉素或塞来昔布处理后荧光显微镜下可观察到典型的细胞凋亡形态变化。与两者单独用药相比,联合用药后的DNA梯度变化更为明显。联合用药48 h后MGC -803细胞堆积在G0/G1,而S期减少的细胞数量比两者分别用药时更为显著。结论:塞来昔布和阿霉素具有协调的诱导凋亡的作用,这对于将COX -2抑制剂用于肿瘤的临床辅助化疗具有重要意义。
OBJECTIVE: To investigate the apoptosis-inducing effect of celecoxib combined with doxorubicin, a cyclooxygenase-2 (COX-2) inhibitor, on gastric cancer MGC-803 cell line and to explore the possible molecular mechanisms of its interaction. Methods: MTT assay was used to detect the proliferation of MGC-803. The apoptosis of tumor cells was detected by fluorescence microscopy, flow cytometry and DNA gradient electrophoresis. Results: With the increase of doxorubicin dose, the number of MGC-803 cells was significantly reduced. Most of the cells were quiescent in G0/G1 phase, and cells in S phase were significantly decreased. Adriamycin (5 mg/L) combined with celecoxib (25 μmol/L) significantly inhibited the growth of MGC-803 cells. After tumor cells were treated with doxorubicin or celecoxib, the typical morphology of apoptosis was observed under fluorescence microscope. Compared with the two drugs alone, the changes in the DNA gradient after combination were more pronounced. After 48 h of combination, MGC-803 cells accumulated in G0/G1, and the number of cells in S phase decreased more significantly than when they were administered separately. CONCLUSIONS: Celecoxib and doxorubicin have coordinated apoptosis-inducing effects, which is of great significance for the use of COX-2 inhibitors in clinical adjuvant chemotherapy of tumors.