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Hepatocellular carcinoma (HCC), ranking as the seventh most prevalent cancer worldwide, poses a significant health challenge. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine, has exhibited promising inhibitory effects on the proliferation, invasion, and migration of various cancer cell types. Nevertheless, its specific impact and underlying mechanisms concerning HCC remain unclear. This research aimed to elucidate the anticancer properties and potential molecular mechanisms of acRoots in the HepG2 and LM3 cell lines. Our findings demonstrate that acRoots effectively hampers the in vitro proliferation, migration, and invasion of HCC cells. Furthermore, acRoots induces apoptosis and autophagy by impeding the AKT/mTOR signaling pathway, with its inhibitory effects on cells being restored under AKT activator induction. This study, for the first time, elucidates that acRoots can suppress HepG2 and LM3 cell proliferation by blocking the Akt/mTOR pathway, thereby activating apoptosis and autophagy. These results underscore the potential of acRoots as a promising antitumor agent for HCC.
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BACKGROUND: The aim of the present study was to investigate the antitumor properties of N-(N-[3,5-difluorophenacetyl]-1-alanyl)-S-phenylglycine t-butyl ester (DAPT) against hepatocellular carcinoma (HCC), as well as the underlying mechanism. METHODS: Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay were used to determine the expression of Notch1 in HCC tissues. The expression of Notch1 in 3 HCC cell lines was evaluated by qRT-PCR and Western blot. The proliferation ability of cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Flow cytometry and Transwell assay were used to check the apoptosis and migration of HepG2 cells, respectively. Western blot was used to determine the expression level of Notch1, Hes1, Phosphatase and tensin homolog (PTEN), protein kinase B1 (AKT1), phosphorylated AKT1, mammalian target of rapamycin (mTOR), phosphorylated mTOR, intracellular adhesion molecule-1, vascular cell adhesion protein 1, matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase in cells and tumor tissues. A HepG2 xenograft experiment was conducted to evaluate the in vivo antitumor properties of DAPT. RESULTS: Notch1 was found to be significantly upregulated in both HCC tissues and cell lines. DAPT significantly inhibited the proliferation and migration of HepG2 cells in a dose-dependent manner, accompanied by the suppression of Notch1/Hes1 signaling, inactivation of AKT/mTOR signaling, downregulation of MMPs, and decreased expression of adhesion molecules. The activation of Notch1/Hes1 or AKT/mTOR signaling removed the inhibitory effect of DAPT on the proliferation and migration of HepG2 cells, as well as the inhibitory properties of DAPT on the expression of MMPs and adhesion molecules. The antitumor properties and regulatory effect of DAPT against the extracellular matrix (ECM) and Hes1/PTEN/AKT/mTOR signaling were verified by the HepG2 xenograft experiments. CONCLUSIONS: DAPT could suppress the proliferation and migration of HCC by regulating the ECM and inhibiting the Hes1/PTEN/AKT/mTOR signaling pathway.
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MicroRNA (miRNA/miR)-3677 has been indicated to be negatively associated with the survival of patients with hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas database. However, as a novel miRNA, the role of miR-3677-5p in HCC has remained to be elucidated. In the present study, the expression of miR-3677-5p was assessed in HCC tissues and cell lines using reverse transcription-quantitative PCR. Survival analysis was performed using Kaplan-Meier curves. Furthermore, the prognostic significance of miR-3677-5p was evaluated using Cox regression analysis. The effects of miR-3677-5p on cell proliferation, as well as migration and invasion capacities, were analyzed using Cell Counting Kit-8, crystal violet and Transwell assays. The results demonstrated that the level of miR-3677-5p expression was upregulated in human HCC tissues and cell lines and that miR-3677-5p expression was closely associated with tumor size, TNM stage and vascular invasion. Furthermore, high miR-3677-5p expression was significantly associated with unfavorable clinical prognosis for patients with HCC. Overexpression of miR-3677-5p was indicated to significantly promote the proliferation, migration and invasion of HCC cells, whereas knockdown of miR-3677-5p was observed to have an inhibitory effect. In conclusion, the present study demonstrated that miR-3677-5p acts as an oncogene that has a critical role in the regulation of HCC proliferation and progression. Hence, miR-3677-5p may serve as a valuable prognostic biomarker and may be developed as a promising therapeutic target for HCC.
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OBJECTIVE: To assess the feasibility and safety of laparoscopic anatomical hepatectomies (LAH) for intrahepatic bile duct stone. METHODS: LAH was performed in 14 patients with intrahepatic bile duct stone, while another 20 patients with intrahepatic bile duct stone underwent classical operation. Surgical time, blood loss, postoperative complications, and postoperative hospital stay were recorded. RESULTS: The operations were successful in all 14 patients who underwent LAH. Surgical time was 190-420 mm [mean (259 +/- 134) mm]. Blood loss during operation was 220-1 000 ml [mean (454.5 +/- 314.2) ml]. No serious postoperative complications occurred. All these 14 patients were discharged with T dragin 7-14 days later, and the mean postoperative hospital stay was (9.2 +/- 3.4) days. In the classical operation group, the surgical time was 125-257 mm [mean (178 +/- 58) mm] and the blood loss was 210-1200 ml [mean (550.9 +/- 348.1) ml] All the patients were discharged with T dragin 9-25 days after operation, and the mean postoperative hospital stay was (13.4 +/- 4.7) days. Surgical time of LAH was longer than classical operation (P < 0.05). Rate of postoperative complications and postoperative hospital stay were decreased in LAH (P < 0.05, P < 0.01). The difference of blood loss during operation was no significance between LAH and classical operation (P > 0.05). CONCLUSIONS: LAH is feasible and safe for selected patients with intrahepatic bile duct stones. As a minimally invasive procedure, it can reduce surgical time, blood loss, hospital stay, and postoperative complications.
