奥沙利铂联合卡培他滨对实验性胃癌大鼠胃癌组织中肿瘤相关因子表达的影响及其协同抗肿瘤作用

doi:10.13481/j.1671-587x.20190407

摘要/Abstract

摘要： 目的：探讨奥沙利铂联合卡培他滨对实验性胃癌大鼠胃癌组织中肿瘤相关因子表达和血清炎症因子水平的影响，阐明其抗肿瘤作用的可能机制。方法：60只Wistar大鼠随机分为对照组、模型组、奥沙利铂组、卡培他滨组和奥沙利铂联合卡培他滨组（联合组），每组12只。采用BGC823胃癌细胞株复制实验性胃癌模型，实验大鼠按分组要求分别给予奥沙利铂（20 mg·kg^-1）和（或）卡培他滨（400 mg·kg^-1），对照组和模型组大鼠给予等体积生理盐水，连续给药8周。测定大鼠肿瘤平均质量，TUNEL染色检测胃癌细胞的凋亡情况，Western blotting法检测大鼠胃癌组织中P53、信号转导与激活因子3（STAT3）和血管内皮生长因子（VEGF）蛋白表达水平，酶联免疫吸附法（ELISA）测定大鼠血清中白细胞介素6（IL-6）、白细胞介素10（IL-10）和肿瘤坏死因子α（TNF-α）水平。结果：与对照组比较，模型组大鼠胃癌组织中P53、STAT3和VEGF蛋白表达水平及血清中IL-6、IL-10和TNF-α水平明显升高（P<0.05）；与模型组比较，奥沙利铂组、卡培他滨组和联合组大鼠肿瘤平均质量及胃癌组织中P53、STAT3和VEGF蛋白表达水平均明显降低（P<0.05），胃癌组织中细胞凋亡指数（AI）明显升高（P<0.05），血清中IL-6、IL-10和TNF-α水平明显降低（P<0.05）；联合组大鼠肿瘤平均质量和胃癌组织中P53、STAT3和VEGF蛋白表达水平及血清中IL-6、IL-10和TNF-α水平明显低于奥沙利铂组和卡培他滨组（P<0.05）。结论：奥沙利铂和卡培他滨能够通过降低大鼠胃癌组织中肿瘤相关因子蛋白表达水平和血清中IL-6、IL-10和TNF-α水平达到抗肿瘤作用，二者联合应用的抗肿瘤作用明显优于单用奥沙利铂或卡培他滨。

关键词: 奥沙利铂, 卡培他滨, 肿瘤相关因子, 胃肿瘤

Abstract: Objective:To investigate the effects of oxaliplatin combined with capecitabine on the expressions of tumor-related factors in the gastric cancer tissue and the levels of serum inflammatory factors in the rats with experimental gastric cancer, and to elucidate the possible mechanism of their anti-tumor effects. Methods:Sixty Wistar rats were randomly divided into control group, model group, oxaliplatin group, capecitabine group and oxaliplatin combined with capecitabine group(combination group);there were 12 rats in each group. The BGC823 cells were used to establish the experimental gastric cancer models. The experimental rats were given capecitabine(400 mg·kg^-1) and(or) oxaliplatin(20 mg·kg^-1) at the same time; the rats in control group and model group were given the normal saline at the same volume for 8 weeks.The average tumor weight was measured after administration. The apoptosis of gastric cancer cells was measured by TUNEL staining. The protein expression levels of P53, signal transduction and activation factor 3(STAT3) and vascular endothelial growth factor(VEGF) in the gastric cancer tissue of the rats in various groups were detected by Western blotting method. The levels of serum interleukin-6(IL-6),interleukin-10(IL-10) and tumor necrosis factor-α(TNF-α) of the rats in various groups were detected by ELISA. Results:Compared with control group, the protein expression levels of P53, STAT3, and VEGF in the gastric cancer tissue and the levels of serum IL-6, IL-10, and TNF-α of the rats in model group were significantly increased (P<0.05). Compared with model group, the average tumor weights and the protein expression levels of P53, STAT3, and VEGF in the gastric cancer tissue and the levels of serum IL-6, IL-10,and TNF-α of the rats in oxaliplatin group, capecitabine group and combination group were significantly decreased (P<0.05); the apoptosis indexes(AI) of gastric cancer cells were significantly increased(P<0.05). The average tumor weight,the protein expression levels of P53, STAT3,and VEGF in gastric cancer tissue and the levels of serum IL-6, IL-10, and TNF-α of the rats in combination group were significantly lower than those in capecitabine group and oxaliplatin group(P<0.05). Conclusion:Both oxaliplatin and capecitabine can paly the anti-tumor effects by reducing the protein expression levels of the tumor-related factors and the serum IL-6, IL-10, and TNF-α levels of the gastric cancer rats, and the anti-tumor effect of combined utilization is better than that of capecitabine or oxaliplatin used alone.

Key words: oxaliplatin, capecitabine, tumore-related factor, stomach neoplasms

中图分类号:

R735.2

袁虎勤, 李强. 奥沙利铂联合卡培他滨对实验性胃癌大鼠胃癌组织中肿瘤相关因子表达的影响及其协同抗肿瘤作用[J]. 吉林大学学报(医学版), 2019, 45(04): 784-789.

YUAN Huqin, LI Qiang. Effects of oxaliplatin combined with capecitabine on expressions oftumor-related factors in gastric cancer tissue of rats with experimental gastric cancer and their synergistic anti-tumor effects[J]. Journal of Jilin University(Medicine Edition), 2019, 45(04): 784-789.

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