Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China.
Beijing Institute of Hepatology, Beijing, People's Republic of China.
Integr Cancer Ther. 2024 Jan-Dec;23:15347354231226126. doi: 10.1177/15347354231226126.
Hepatocellular carcinoma (HCC) is a common clinical malignant tumor of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients with hepatocellular carcinoma and improve the quality of patients' survival, but its antitumor biological mechanism is still unclear.
A nude mouse hollow fiber hepatocellular carcinoma model was constructed to analyze the in vivo efficacy of HQZX decoction against 7 different hepatocellular carcinoma cells. The subcutaneous graft tumor model was again validated. In vitro, the effect of HQZX decoction on the growth and metastasis of the cell line with the highest growth inhibition was evaluated. The cell line with the best efficacy response screened was again used to construct a hollow fiber hepatocellular carcinoma model and hollow fiber conduit cells were extracted to detect the expression of HIF-1α, VEGF, EMT-related molecules, LCSCs-related molecules, and to observe the density of the subcutaneous vascular network of hollow fiber conduits. The liver metastasis model of splenic injection was constructed to observe the effect of HQZX decoction on tumor metastasis.
The hollow fiber hepatocellular carcinoma model was evaluated for the efficacy of HQZX decoction, and it was found to have the highest growth inhibition of LM3-luc cells. In vitro, the CCK8 assay revealed that HQZX decoction could inhibit tumor migration and invasion and promote apoptosis. In addition, the mechanism study of extracting cells from hollow fiber tubes found that HQZX decoction could inhibit metastasis-associated HIF-1α, VEGF, EMT-related molecules, and LCSCs-related molecules expression. capillary network around subcutaneous fiber tubes was reduced in the HQZX decoction gavage group of mice. It inhibited tumor metastasis in nude mice.
HQZX decoction inhibited the growth of a variety of hepatocellular carcinoma cells. HQZX decoction suppressed the expression of metastasis-associated VEGF, EMT-related molecules, and LCSCs-related molecules and inhibited tumor angiogenesis and growth and metastasis, which may be related to the inhibition of the HIF-1α signaling pathway. It reveals that HQZX decoction may be a promising herbal compound for anti-HCC therapy, and also reveals the accurate feasibility of the hollow fiber hepatocellular carcinoma model for in vivo pharmacodynamic evaluation and mechanism study.
肝细胞癌(HCC)是消化系统常见的恶性肿瘤。临床发现胡启正消汤能延长肝癌患者的生存时间,提高患者的生存质量,但抗肿瘤的生物学机制尚不清楚。
构建裸鼠中空纤维肝癌模型,分析胡启正消汤对 7 种不同肝癌细胞的体内疗效。再次验证皮下移植瘤模型。体外评价胡启正消汤对生长抑制率最高的细胞系生长和转移的影响。再次筛选疗效反应最好的细胞系,构建中空纤维肝癌模型,提取中空纤维管细胞,检测 HIF-1α、VEGF、EMT 相关分子、LCSCs 相关分子的表达,观察中空纤维管皮下血管网络密度。构建脾注射肝转移模型,观察胡启正消汤对肿瘤转移的影响。
评估胡启正消汤对中空纤维肝癌模型的疗效,发现对 LM3-luc 细胞的生长抑制作用最强。体外 CCK8 检测结果表明,胡启正消汤能抑制肿瘤迁移和侵袭,促进凋亡。此外,从中空纤维管提取细胞的机制研究发现,胡启正消汤能抑制转移相关的 HIF-1α、VEGF、EMT 相关分子和 LCSCs 相关分子的表达。胡启正消汤灌胃组小鼠皮下纤维管周围毛细血管网络减少,抑制裸鼠肿瘤转移。
胡启正消汤抑制多种肝癌细胞生长。胡启正消汤抑制转移相关 VEGF、EMT 相关分子和 LCSCs 相关分子的表达,抑制肿瘤血管生成和生长转移,可能与抑制 HIF-1α 信号通路有关。这表明胡启正消汤可能是一种很有前途的抗肝癌治疗中草药,也揭示了中空纤维肝癌模型在体内药效评价和机制研究中的准确可行性。