| 引用本文: |
李阳, 张洽淳, 陈蕾, 莫潘艳, 黄国栋, 王济国, 曾超.基于MAPK通路探讨三虫通络散结方对Lewis肺癌小鼠的抑瘤作用[J].湖南中医药大学学报,2024,44(12):2164-2171[点击复制] |
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| 基于MAPK通路探讨三虫通络散结方对Lewis肺癌小鼠的抑瘤作用 |
| 李阳,张洽淳,陈蕾,莫潘艳,黄国栋,王济国,曾超 |
| (广州中医药大学第七临床医学院, 广东 深圳 518100) |
| 摘要: |
| 目的 研究三虫通络散结方对Lewis肺癌小鼠的抑瘤作用及对丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路的调控作用。方法 选取C57BL/6小鼠48只，随机挑选6只作为空白组；42只C57BL/6小鼠构建Lewis肺癌荷瘤小鼠模型，随机分为模型组（生理盐水）、阳性对照组（顺铂注射液2 mg/kg）、散剂低剂量组（三虫通络散结方散剂0.45 g/kg）、散剂高剂量组（三虫通络散结方散剂1.8 g/kg）、散剂低剂量+顺铂组（三虫通络散结方散剂0.45 g/kg+顺铂注射液2 mg/kg）、汤剂低剂量组（三虫通络散结方汤剂3.9 g/kg）、汤剂高剂量组（三虫通络散结方汤剂15.6 g/kg），每组6只，给药14 d后取材。计算抑瘤率和去瘤体质量；HE染色观察皮下移植瘤体、肺组织、肝组织的病理变化；qPCR检测皮下移植瘤细胞外调节蛋白激酶（extracellular regulated protein kinases,Erk）、缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）、p38、血管内皮生长因子A（vascular endothelial growth factor A,VEGFA）、c-Jun氨基末端激酶（c-Jun N-terminal kinase,JNK）、基质金属蛋白酶-2（matrix metalloproteinase-2,MMP-2） mRNA的表达量；Western blot检测皮下移植瘤Erk、HIF-1α、p38、VEGFA、JNK、MMP-2蛋白表达情况。结果 （1）与模型组相比，阳性对照组、散剂低剂量+顺铂组、散剂高剂量组瘤体质量降低（P＜0.05）。与散剂低剂量组相比，散剂高剂量组瘤体质量降低（P＜0.05）。与阳性对照组相比，各中药单药组及模型组去瘤体质量升高（P＜0.05）。（2）各组小鼠肺组织HE染色结果显示，散剂低剂量+顺铂组见较多肿瘤细胞坏死；各中药组细胞均少见核分裂，肿瘤转移灶较模型组少。各组小鼠肝组织HE染色结果显示，散剂低剂量+顺铂组、阳性对照组未见明显肿瘤病灶形成；散剂高剂量组、汤剂高剂量组的肿瘤转移灶体积相对较小。（3）与模型组相比，其余各荷瘤组皮下移植瘤组织中Erk、p38 mRNA表达下降（P＜0.05），散剂低剂量+顺铂组、散剂低剂量组、汤剂低剂量组、汤剂高剂量组JNK mRNA表达下降（P＜0.05）；与阳性对照组相比，散剂低剂量+顺铂组及各中药组皮下移植瘤组织中JNK mRNA表达下降（P＜0.05）。（4）与模型组相比，阳性对照组、散剂低剂量组、汤剂高剂量组Erk蛋白表达水平降低（P＜0.05），阳性对照组、散剂低剂量+顺铂组、散剂低剂量组、散剂高剂量组、汤剂高剂量组p38、HIF-1α蛋白表达水平降低（P＜0.05），其余各荷瘤组JNK蛋白表达水平均降低（P＜0.05）。结论 三虫通络散结方对Lewis肺癌小鼠有一定的抑瘤作用，以散剂高剂量组抑瘤效果较优，其机制可能是与抑制MAPK信号通路相关。 |
| 关键词: Lewis肺癌细胞 三虫通络散结方 肺癌 MAPK信号通路 抑瘤作用 |
| DOI：10.3969/j.issn.1674-070X.2024.12.004 |
| 投稿时间：2024-06-06 |
| 基金项目:广东省中医药管理局项目（20231294）;深圳市宝安区科创局项目（2021JD145）;深圳市宝安区引进高层次医学团队项目资助项目（202403）;深圳市宝安区2024年度区属公立医院高质量发展研究项目（BAGZL2024119）。 |
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| Tumor inhibitory effects of Sanchong Tongluo Sanjie Formula on Lewis lung cancer mice based on MAPK pathway |
| LI Yang, ZHANG Qiachun, CHEN Lei, MO Panyan, HUANG Guodong, WANG Jigou, ZENG Chao |
| (The Seventh Clinical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518100, China) |
| Abstract: |
| Objective To study the tumor inhibitory effects of Sanchong Tongluo Sanjie Formula (SCTLSJF) on Lewis lung cancer mice and its regulatory effects on the mitogen-activated protein kinase (MAPK) signaling pathway. Methods A total of 48 C57BL/6 mice were selected, and six of them were randomly assigned to the blank group. The remaining 42 C57BL/6 mice were used to establish the Lewis lung cancer-bearing mouse model, and were then randomized into model group (normal saline), positive control group (Cisplatin Injection 2 mg/kg), low-dose powder group (SCTLSJF powder 0.45g/kg), high-dose powder group (SCTLSJF powder 1.8 g/kg), low-dose powder+cisplatin group (SCTLSJF powder 0.45 g/kg+Cisplatin Injection 2 mg/kg), low-dose decoction group (SCTLSJF decoction 3.9 g/kg), and high-dose decoction group (SCTLSJF decoction 15.6 g/kg), with six mice in each group. Samples were collected 14 days after administration. The tumor suppression rate and tumor-free body mass were calculated. HE staining was used to observe the pathological changes of the subcutaneous xenograft tumor, lung tissues, and liver tissues; qPCR was employed to determine the mRNA expressions of extracellular regulated protein kinases (Erk), hypoxia inducible factor-1α (HIF-1α), p38 protein (p38), vascular endothelial growth factor A (VEGFA), c-Jun N-terminal kinase (JNK), and matrix metalloproteinase 2 (MMP-2) in the subcutaneous xenograft tumor, while Western blot to examine the protein expressions of them. Results (1) Compared with the model group, the xenograft tumor mass in the positive control, low-dose powder+cisplatin, and high-dose powder groups was lower (P<0.05). Compared with the low-dose powder group, the xenograft tumor mass was lower in the high-dose powder group (P<0.05). Compared with the positive control group, the tumor-free body mass was higher in all pure Chinese medicine groups and model group (P<0.05). (2) The HE staining of lung tissues showed that the low-dose powder+cisplatin group exhibited a higher degree of tumor cell necrosis; in all pure Chinese medicine groups, nuclear division was rarely observed, and the number of tumor metastases was lower compared to the model group. The HE staining of liver tissues showed that no significant tumor lesions were observed in the low-dose powder+cisplatin and positive control groups; the tumor metastasis foci in the high-dose powder and high-dose decoction groups were relatively small in volume. (3) Compared with the model group, the mRNA expressions of Erk and p38 in the subcutaneous xenograft tumor tissues in the other cancer-bearing groups decreased (P<0.05). The expression of JNK mRNA also decreased in the low-dose powder+cisplatin, low-dose powder, low-dose decoction, and high-dose decoction groups (P<0.05). Compared with the positive control group, the low-dose powder+cisplatin group and all pure Chinese medicine groups showed a decrease in JNK mRNA expression in the subcutaneous xenograft tumor tissues (P<0.05). (4) Compared with the model group, the protein expression level of Erk decreased in the positive control, low-dose powder, and high-dose decoction groups (P<0.05), the protein expression levels of p38 and HIF-1α decreased in the positive control, low-dose powder+cisplatin, low-dose powder, high-dose powder, and high-dose decoction groups (P<0.05), and the protein expression level of JNK decreased in the other cancer-bearing groups (P<0.05). Conclusion SCTLJSF has certain inhibitory effects on Lewis lung cancer in mice, with the high-dose powder group showing the superior tumor inhibitory efficacy. The mechanism may be related to the inhibition of MAPK signaling pathway. |
| Key words: Lewis lung cancer cells Sanchong Tongluo Sanjie Formula lung cancer mitogen-activated protein kinase signaling pathway tumor inhibitory effects |
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