柴胡皂苷D联合奥沙利铂对A549细胞荷瘤裸鼠的抑瘤作用及其机制
Antitumor activity and mechanism of saikosaponin D combined with oxaliplatin on A549 cells-bearing nude mice
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摘要: 考察柴胡皂苷D联合奥沙利铂对荷人肺腺癌A549细胞裸鼠的抑瘤作用及其机制。建立A549细胞荷瘤小鼠模型，灌胃给予柴胡皂苷D，以体内抑瘤率考察柴胡皂苷D的最佳剂量，再考察柴胡皂苷D与奥沙利铂联合用药对肿瘤的生长状态的影响，TUNEL法检测凋亡细胞，ELISA法检测血清中前列腺素E2(PGE2)浓度变化，Western blot检测瘤体中COX-2蛋白的表达。结果显示:柴胡皂苷D 在1.0 mg/kg时抑制作用最佳(抑瘤率40.96%)；柴胡皂苷D与奥沙利铂联合用药诱导荷瘤裸鼠瘤体凋亡的作用强于二者单独用药；荷瘤模型组PGE2浓度和COX-2的表达明显增高；单独和联合用药PGE2浓度、COX-2表达量均显著降低(P<；0.05)，且联合用药组的PGE2浓度和COX-2表达均显著低于单用组(P<；0.01)。研究结果表明，柴胡皂苷D联合奥沙利铂用药能产生协同作用，其抑瘤作用可能是通过下调COX-2蛋白的表达来实现的。Abstract: This study was to investigate the effect and mechanism of saikosaponin D(SSD)combined with oxaliplatin on nude mice bearing human lung carcinoma A549 cells. The A549 cell-bearing nude mice model was established and then the optimal dosage of SSD for intragastric administration was valued by tumor inhibitory ratio in vivo. The effect of SSD combined with oxaliplatin on tumor growth in A549 cells-bearing nude mice was observed. The apoptosis was detected by TUNEL method, the concentration of prostaglandin E2(PGE2)in plasma was checked by ELISA method, and the expression of COX-2 in tumor was analyzed by Western blot. The result showed that SSD exerted best tumor inhibitory effect(40. 96%)at the dosage of 1. 0 mg/kg. SSD combined with oxaliplatin group induced better apoptosis effect in A549 cells-bearing nude mice than those of SSD group and oxaliplatin group, respectively. The concentration of PGE2 and the expression of COX-2 in model group were increased markedly, while decreased significantly in SSD, oxaliplatin or SSD combined with oxaliplatin treated groups(P< 0. 05), and the concentration of PGE2 and the expression of COX-2 in SSD combined with oxaliplatin group were significantly lower than those treated by SSD or oxaliplatin alone(P< 0. 01). In conclusion, SSD combined with oxaliplatin could exert synergistic effect to induce apoptosis of A549 cells in nude mice, which may achieved by down-regulation of the expression of COX-2.
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Keywords:
- saikosaponin D /
- oxaliplatin /
- drug combination /
- A549 cells /
- inhibitory effect
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