不平衡氨基酸对肿瘤细胞生长和细胞凋亡的影响

Influence of imbalance amino acids on apoptosis in tumor-bearing rats

目的比较几种不平衡氨基酸营养支持对肿瘤生长和细胞凋亡的影响。方法荷W alker-256癌肉瘤SD大鼠,空肠喂饲肠外营养制剂10 d,据所喂饲制剂中氨基酸组成的不同分为:A组(平衡氨基酸组)、B组(增量精氨酸不平衡氨基酸组)、C组(去蛋氨酸不平衡氨基酸组)、D组(去缬氨酸不平衡氨基酸组)、E组(增量精氨酸、去蛋氨酸、去缬氨酸不平衡氨基酸组)。肿瘤体积增长速度、肿瘤质量、肿瘤质量/尸重,肿瘤组织PCNA指数,肿瘤细胞周期各时相百分比以及DNA倍性作为观察肿瘤生长速度的指标,并观察肿瘤细胞凋亡状况。结果上述各肿瘤生长指标值显示:B、C、D组与A组相比,除DNA倍性外,其余各指标值均降低(P<0.01),但B、C、D组间比较差异无显著性(P>0.05)。E组与B、C、D组相比较,所有指标值均显著降低(P<0.05);A、B、C、D、E组细胞凋亡指数分别为:(6.5±1.4)%、(13.7±2.8)%、(12.9±3.1)%、(14.1±4.4)%、(28.9±6.5)%,E组较A、B、C、D组凋亡指数明显升高,B、C、D组较A组亦升高明显(P<0.01),、B、C、D组间差异无显著性。结论平衡氨基酸促进肿瘤生长;增量精氨酸、去蛋氨酸、去缬氨酸3种不平衡氨基酸对肿瘤生长有同等抑制作用并诱导肿瘤细胞凋亡;增量精氨酸、去蛋氨酸、去缬氨酸复合不平衡氨基酸对肿瘤生长抑制及诱导肿瘤细胞凋亡作用更显著。

Objective To study effects of imbalance amino acids nutrition support on apoptosis and tumor growth in tumor -bearing rats. Methods Parenteral nutritional solution had been fed for 10 days by jejumostomy in rats bearing Walker - 256 carcinosarcoma. The tumor- bearing rats were divided into five different groups according to formulas of amino acids in parenteral nutritional solution respectively ： group A （ balance amino acid）, group B （ arginine - enriched amino acid ）, group C （ methionine - depleted amino acid）, group D （valine -depleted amino acid） and group E （complex amino acids of arginine -enriched, methionine- depleted and valine - depleted ）. Indices of tumor growth： tumor volume, tumor weight, tumor weight/carcass body weight, the expression of proliferating cell nuclear antigen （ PCNA）, DNA ploidy and cell cycle of tumor tissue were investigated; the rate of apoptosis of tumor cells was evaluated with flow cytometry and DAPI staining. Results The levels of above indices except DNA ploidy were as the following： group B, C and D were significantly lower than group A （ P 〈0. 01 ）, but there were no significant difference among group B, C and D （ P 〉 0. 05 ）. All tumor growth indices of group E were significantly less than those of group B, C and D （ P 〈 0. 05 ）. Apoptosis index of group A, B, C, D and E were （6.5 ±1.4）%,（13.7 ±2.8）%, （12.9±3.1）%, （14.1 ±4.4）%, and （28.9±6.5）% respectively ; apoptosis index of group E were significantly higher than those of group B, C and D （ P 〈0.05 ）, apoptosis index of group A were significantly less than those of group B, C and D （ P 〈 . 05 ）. Conclusions Balance amino acid stimulates tumor growth; arginine enriched, methionine-depleted and valine-depleted amino acids inhibit tumor growth and induces apoptosis of tumor cell; and complex amino acids of arginine-enriched, methionine - depleted and valine-depleted have stronger inhibitory effect on tumor growth.