QHF-顺铂在小鼠模型中抗肝细胞癌的机制

Mechanism of QHF-cisplatin against hepatocellular carcinoma in a mouse model.

作者信息

Chen Tao, Yuan Shen-Jun, Wang Jing, Hu Wei

机构信息

Tao Chen, Wei Hu, the Third Level of TCM Pharmacology Research Laboratory affiliated to China TCM Administration, Medical Science College of China Three Gorges University, Yichang 443002, Hubei Province, China.

出版信息

World J Gastroenterol. 2015 Sep 21;21(35):10126-36. doi: 10.3748/wjg.v21.i35.10126.

DOI:10.3748/wjg.v21.i35.10126

PMID:26401077

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4572793/

Abstract

AIM

To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma (HCC) and their mechanisms of action.

METHODS

Sixty BALB/c mice were randomly divided into a model group (n = 48) and a normal control group (n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP (cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under an optical microscope. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels in serum were measured. Hepatocyte growth factor (HGF), c-mesenchymal-epithelial transition (c-Met) factor, phosphorylated (p)-c-Met, p38, p-p38, extracellular signal-regulated kinase (ERK), p-ERK and vascular endothelial growth factor (VEGF) levels were evaluated in tumor and liver tissues using western blotting.

RESULTS

Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group (0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant (P < 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group (P < 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups (P < 0.05).

CONCLUSION

QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.

摘要

目的

研究芪黄扶正（QHF）联合顺铂对H22肝癌（HCC）的影响及其作用机制。

方法

将60只BALB/c小鼠随机分为模型组（n = 48）和正常对照组（n = 12）。通过将H22细胞直接注射到小鼠肝实质内建立HCC异种移植瘤模型。模型组的48只BALB/c小鼠随机分为四组：芪黄扶正组、顺铂（DDP）组、芪黄扶正联合顺铂组和模型对照组。通过计算肿瘤生长抑制率评估这些药物对肿瘤生长的抑制作用。观察小鼠的一般状况、体重和生存时间进行检查。在光学显微镜下观察肿瘤组织的变化。检测血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和甲胎蛋白（AFP）水平。采用蛋白质免疫印迹法检测肿瘤和肝组织中肝细胞生长因子（HGF）、c-间质-上皮转化（c-Met）因子、磷酸化（p）-c-Met、p38、磷酸化p38、细胞外信号调节激酶（ERK）、磷酸化ERK和血管内皮生长因子（VEGF）水平。

结果

与顺铂组相比，芪黄扶正联合顺铂组的毒副反应发生率较低，生存时间较长。芪黄扶正组、顺铂组和芪黄扶正联合顺铂组的肿瘤重量均显著低于模型对照组（分别为0.24±0.07、0.18±0.03和0.14±0.01 g vs 0.38±0.05 g），差异具有统计学意义（P < 0.01）。芪黄扶正组、顺铂组和芪黄扶正联合顺铂组的肿瘤生长抑制率分别为38.7%、52.6%和63.5%。芪黄扶正组、顺铂组和芪黄扶正联合顺铂组血清中的AST、ALT和AFP水平均显著低于模型对照组（P < 0.05）。同样，芪黄扶正组、顺铂组和芪黄扶正联合顺铂组肿瘤组织中的HGF、p-c-Met、磷酸化p38、磷酸化ERK和VEGF水平均显著降低（P < 0.05）。