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目的:通过体内、体外实验,探讨γ-氨基丁酸(γ-aminobutyric acid,GABA)对结直肠癌SW480、HCT116细胞的抑制作用及其与化疗联用的增敏作用。方法:采用CCK-8方法分析GABA及其与抗癌药5-氟尿嘧啶(5-fluorouracil,5-FU)或奥沙利铂(Oxaliplatin,OXA)联用对结直肠癌SW480、HCT116细胞增殖的影响,流式细胞术分析GABA对SW480、HCT116细胞周期的影响。通过裸鼠成瘤实验观察移植瘤质量和体积,免疫组化法检测裸鼠肿瘤组织Ki67蛋白的表达,TUNEL染色观察裸鼠结直肠癌细胞的凋亡,体内实验研究GABA与OXA联用对肿瘤细胞生长的影响。结果:100μmol/L GABA可显著抑制结直肠癌SW480、HCT116细胞的增殖,其抑制率分别为(37.38±2.62)%、(15.54±1.33)%,GABA浓度增加至200μmol/L时,其抑制作用未见明显增强。GABA使SW480、HCT116细胞S期数量分别减少11.8%及10.7%。GABA与5-FU或OXA联用组对SW480细胞增殖抑制率高于5-FU或OXA组[(72.76±1.07)%vs(63.82±3.29)%或(65.60±1.19)%vs(57.09±1.25)%;q=4.079或4.128,P<0.05],对HCT116细胞增殖抑制率也高于单用5-FU及OXA组[(79.53±1.12)%vs(69.71±0.09)%或(73.19±0.07)%vs(64.65±1.99)%;q=4.569或4.561,P<0.05]。实验结束时,GABA与OXA联用组小鼠移植瘤质量、体积显著低于对照组和OXA组[(0.20±0.016)vs(0.42±0.039)、(0.36±0.030)g和(250±27)vs(780±60)、(520±46)mm~3,均P<0.01];抑制Ki67蛋白在肿瘤组织的表达、促进肿瘤组织细胞的凋亡。结论:GABA对结直肠癌细胞增殖具有较强的抑制作用,与5-FU或OXA联用可增强化疗效果。
OBJECTIVE: To investigate the inhibitory effect of γ-aminobutyric acid (GABA) on colorectal cancer SW480 and HCT116 cells and its sensitization to chemotherapy in vitro and in vivo. Methods: The effects of GABA and its combination with anticancer agent 5-fluorouracil (5-FU) or oxaliplatin (OXA) on the proliferation of colorectal cancer SW480 and HCT116 cells were analyzed by CCK-8 assay , Flow cytometry analysis of GABA SW480, HCT116 cell cycle. The transplanted tumor mass and volume were observed by nude mouse tumorigenicity assay. The expression of Ki67 protein in tumor tissue was detected by immunohistochemistry. TUNEL staining was used to observe the apoptosis of colorectal cancer cells in nude mice. In vivo, GABA combined with OXA Effect of cell growth. Results: 100μmol / L GABA could significantly inhibit the proliferation of colorectal cancer SW480 and HCT116 cells with the inhibitory rates of (37.38 ± 2.62)% and (15.54 ± 1.33)%, respectively. When GABA concentration was increased to 200μmol / L, No significant increase. GABA reduced the number of S phase of SW480 and HCT116 cells by 11.8% and 10.7% respectively. The inhibitory rate of GABA combined with 5-FU or OXA on SW480 cells was higher than that of 5-FU or OXA group [(72.76 ± 1.07)% vs (63.82 ± 3.29)% or (65.60 ± 1.19)% vs (57.09 ± 1.25) (79.53 ± 1.12)% vs (69.71 ± 0.09)% or (73.19 ± 0.07)% respectively in the 5-FU group and the OXA group (q = 4.079 or 4.128, P <0.05) )% vs (64.65 ± 1.99)%; q = 4.569 or 4.561, P <0.05]. At the end of the experiment, the mass and volume of transplanted tumor in GABA plus OXA group were significantly lower than those in control group and OXA group [(0.20 ± 0.016) vs (0.42 ± 0.039), (0.36 ± 0.030) and (250 ± 27) vs (780 ± 60), (520 ± 46) mm ~ 3, all P <0.01]; inhibited the expression of Ki67 protein in tumor tissues and promoted the apoptosis of tumor cells. Conclusion: GABA has a strong inhibitory effect on the proliferation of colorectal cancer cells. Combined with 5-FU or OXA, GABA can enhance the effect of chemotherapy.