5-氟尿嘧啶气雾对人胃癌细胞MKN-45增殖、凋亡及周期的影响

Effect of 5-fluorouracil aerosol on the growth of human gastric cancer cell line MKN-45 in vitro

目的通过体外模拟5-氟尿嘧啶(5-Fu)腹腔气雾化疗环境,评价5-Fu雾化对人胃癌细胞MKN-45增殖、凋亡及周期的影响。方法运用自主研发的气雾化疗仪将5-Fu雾化,体外模拟腹腔气雾化疗环境,对胃癌细胞进行处理,维持气雾环境压力为8mmHg,作用时间为30min,并设生理盐水雾化作为对照,处理后用MTT法检测细胞增殖情况,流式细胞仪检测细胞凋亡和细胞周期。结果 MTT结果显示,5-Fu气雾化疗组杀伤率显著高于生理盐水组[(31.13±3.51)%比(4.65±1.99)%,P<0.001];流式细胞结果显示,与生理盐水组相比,5-Fu气雾化疗组细胞凋亡率升高[(12.00±0.92)%比(2.65±0.52)%,P<0.001)],G1期细胞增多[(51.83±1.95)%比(36.41±2.33)%,P<0.001]、S期细胞减少[(16.72±2.36)%比(45.20±3.27)%,P<0.001],差异均有统计学意义。结论 5-Fu气雾能有效抑制胃癌细胞的增殖并诱导凋亡,使细胞阻滞于G1期,为气雾化疗的临床应用提供实验依据。

Objective To evaluate the effect of simulated intraperitoneal 5-fluorouracil （5-Fu） aerosol chemotherapy （AIPC） on the proliferation, apoptosis, and cell cycle of human gastric cancer cell line MKN-45 in vitro. Methods The gastric cancer cells MKN-45 were treated with 5-Fu aerosol for 30 min under the pressure of 8 mmHg, and those treated with normal saline （NS） aerosol served as the control. The cell proliferation after the treatment was detected by MTT assay, and flow cytometry and FITC Annexin V/PI kit were used to detect the cell apoptosis and changes in the cell cycle. Results MTT assay showed a significantly greater inhibition rate of the cell proliferation in 5-Fu aerosol group than in NS group [（31.13±3.51）% vs （4.65±1.99）%, P〈0.001]. FCM analysis also showed a significantly higher cell apoptotic rate in 5-Fu aerosol group than in NS group [（12.00±0.92）% vs （2.65±0.52）%, P〈0.001]. Compared with saline treatment, treatment with 5-Fu aerosol resulted in a greater proportion of G1 phase cells [（51.83±1.95）% vs （36.41±2.33）%, P〈0.001] with a lowered proportion of S phase cells [（16.72±2.36）% vs （45.20±3.27）%, P〈0.001]. Conclusion Simulated 5-Fu AIPC can inhibit the proliferation, induce cell apoptosis and cause cell cycle arrest at G1 phase in gastric cancer cells