关键词: 脱氢卡维丁, 索拉非尼, 肝细胞癌, 迁移和侵袭

Abstract:

Objective To investigate the effects of different doses of dehydrocavidine （DHC） used as a single agent on the in vitro proliferation， migration， and invasion capabilities of human hepatocellular carcinoma Huh7 cells， as well as the in vivo tumor-forming capacity of mouse hepatocellular carcinoma Hep1-6 cells. Simultaneously， to clarify the differences in anticancer efficacy between DHC and sorafenib and the synergistic effects of combination therapy， thus providing experimental evidence for the treatment of hepatocellular carcinoma （HCC）. Methods Human hepatocellular carcinoma Huh7 cells were treated with DHC at gradient concentrations of 0.1， 0.2， and 0.3 mg/mL. Cell proliferation was assessed using the CCK-8 assay. Meanwhile， cell colony formation， migration， and invasion were evaluated using plate cloning， cell scratch， and Transwell assays， respectively. A suspension of Hep1-6 cells in the logarithmic growth phase was subcutaneously injected into the right axilla of BALB/c-nu nude mice to establish a subcutaneous liver cancer xenograft model. Once the tumour volume had reached approximately 30 mm³， the nude mice bearing xenografts were randomly divided into a control group， low-dose， medium-dose， and high-dose DHC groups to conduct an in vivo dose-response study of DHC monotherapy. Once the effective dose of DHC had been determined， additional groups were established， including a control group， a DHC monotherapy group， a sorafenib monotherapy group， and a DHC-sorafenib combination group， to conduct experiments comparing the efficacy of individual drugs and combination therapy. All groups were administered the drugs regularly via intraperitoneal injection every other day. During the experiment， the major and minor axes of the tumours were periodically measured to calculate tumour volume， and changes in the body weight of the nude mice were continuously monitored. Results DHC demonstrated a concentration- and time-dependent inhibitory effect on the proliferation of Huh7 cells （P < 0.05）. In all concentration groups， the wound healing width， the number of colony-forming units， and the number of cells crossing the membrane were significantly lower compared to the control group （P < 0.05）. In the in vivo single-agent administration experiments， the tumour volumes in all DHC dose groups were significantly smaller than those in the control group （P < 0.05）， showing a dose-dependent relationship. In the combination therapy experiments， the tumour volumes in the DHC and sorafenib group， the DHC monotherapy group， and the sorafenib monotherapy group were all significantly smaller than those in the control group （P < 0.05）. There were no statistically significant differences in the body weight among the groups of nude mice （P > 0.05）， and no obvious toxicity was observed. Conclusion DHC can inhibit， in a dose-dependent manner， the in vitro malignant phenotype of human hepatocellular carcinoma Huh7 cells and the in vivo tumourigenic capacity of mouse hepatocellular carcinoma Hep1-6 cells.

Key words: dehydrocavidine, sorafenib, hepatocellular carcinoma, migration and invasion