| 摘要: |
| 目的：观察解毒扶正方对分子靶向药物获得性耐药非小细胞肺癌小鼠模型的干预作用。方法：选取BALB/C nu/nu小鼠40只，皮下接种人非小细胞肺癌细胞株PC9/GR成瘤构建皮下移植瘤，随机分为5组，即空白对照组、低剂量+阳性组、高剂量+阳性组、高剂量组、阳性对照组，每组各8只。所有动物经口灌胃给药，灌胃剂量：中药（解毒扶正方）低剂量为52 g生药/kg体质量，中药高剂量为104 g生药/kg体质量，阳性药物（吉非替尼）为51.38 mg/kg体质量，空白对照组给予纯化水灌胃，每天1次，连续15 d。观察各组的瘤体体积、肿瘤生长抑制率，观察瘤体组织，计算肿瘤细胞增殖指数，免疫组化法检测蛋白激酶B（AKT）、磷酸化蛋白激酶B（p-AKT）、细胞外信号调节激酶（ERK）、磷酸化细胞外信号调节激酶（p-ERK）及核因子E2相关因子2（Nrf2）表达水平，计算p-ERK/ERK、p-AKT/AKT值。结果：瘤体体积、肿瘤生长抑制率高剂量组、高剂量+阳性组与空白对照组比较，差异具有统计学意义（P＜0.05）；低剂量+阳性组、高剂量+阳性组、高剂量组肿瘤细胞增殖指数以及肿瘤组织p-ERK/ERK与空白对照组比较，差异具有统计学意义（P＜0.05或P＜0.01）。结论：解毒扶正方可缩小分子靶向药物获得性耐药非小细胞肺癌裸鼠皮下移植瘤模型体积，抑制皮下移植瘤生长，降低肿瘤细胞增殖指数，降低p-ERK/ERK比值，升高Nrf2蛋白表达。 |
| 关键词: 非小细胞肺癌 分子靶向治疗 获得性耐药 解毒扶正方 实验研究 |
| DOI： |
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| Discuss the Intervention effect of Jiedu Fuzheng prescription on a mouse model of lung cancer with acquired drug-resistance to molecular-targeted therapy |
| WANG Wei,DENG Tianhao,JIN Zhaohui |
| (The First Affiliated Hospital of Hunan University of Chinese Medicine，Changsha 410007，Hunan，China;The Affiliated Hospital of Hunan Academy of Chinese Medicine，Changsha 410006，Hunan，China) |
| Abstract: |
| Objective：To investigate the intervention effect of Jiedu Fuzheng prescription on a mouse model of non-small cell lung cancer with acquired drug-resistance to molecular-targeted therapy.Methods：A total of 40 BALB/C nu/nu mice were subcutaneously inoculated with the human non-small cell lung cancer cell line PC9/GR to establish a model of subcutaneous xenograft tumor，and then the mice were randomly divided into blank control group，low-dose+positive group，high-dose+positive group，high-dose group，and positive control group，with 8 mice in each group.All mice were given the drugs by gavage，at a dose of Jiedu Fuzheng prescription 52 g (crude drug)/kg for the low-dose group，Jiedu Fuzheng prescription 104 g (crude drug)/kg for the high-dose group，and positive drug (gefitinib) 51.38 mg/kg，and those in the blank control group were given purified water by gavage，once a day for 15 consecutive days.Tumor volume and tumor growth inhibition rate were calculated for each group；tumor tissue was observed and tumor cell proliferation index was calculated；immunohistochemistry was used to measure the expression levels of protein kinase B (AKT)，phosphorylated AKT (p-AKT)，extracellular signal-regulated kinase (ERK)，phosphorylated ERK (p-ERK)，and nuclear factor erythroid 2-related factor 2 (Nrf2)，and p-ERK/ERK and p-AKT/AKT ratios were calculated.Results：There were significant differences in tumor volume and tumor growth inhibition rate between the high-dose group/the high-dose+positive group and the blank control group (P<0.05).There were also significant differences in tumor cell proliferation index and p-ERK/ERK in tumor tissue between the low-dose+positive group/high-dose+positive group/high-dose group and the blank control group (P<0.05 or P<0.01).Conclusion：In nude mice with non-small cell lung cancer with acquired drug resistance to molecular-targeted therapy，Jiedu Fuzheng prescription can reduce the volume of subcutaneous xenograft tumor，inhibit the growth of subcutaneous xenograft tumor，reduce tumor cell proliferation index and p-ERK/ERK ratio，and improve the protein expression of Nrf2. |
| Key words: non-small cell lung cancer molecular-targeted therapy acquired drug resistance Jiedu Fuzheng prescription experimental study |
