Effects of sinomenine on a rat orthotopic liver carcinoma model

Histol Histopathol. 2024 Jun;39(6):795-804. doi: 10.14670/HH-18-683. Epub 2023 Nov 30.

Abstract

Objective: Liver carcinoma is a common malignant tumor. In this study, an orthotopic liver carcinoma model was established by B-ultrasound, and the therapeutic effect of sinomenine (Sin) on the disease was investigated.

Methods: SD rats were randomly divided into control, Sin, Sorafenib (Sor), and combination (Sin+Sor) groups (n=8). An orthotopic liver carcinoma model was established by inoculating N1-S1 cells into the rat liver by B-ultrasound-guided, and tumor volume was monitored three times by B-ultrasound after inoculation. After drug treatment, the tumor tissues were stained with HE and TUNEL, and the levels of inflammatory cytokines, ALT and AST were detected by ELISA. The numbers of erythrocytes, leukocytes and platelets were detected. Immunohistochemistry and immunofluorescence were used to detect the expression of Ki-67, CD44, VEGF and CD31. The levels of cell cycle, apoptosis-related proteins were detected by western blot.

Results: B-ultrasound monitoring found that Sin reduced tumor volume. Moreover, Sin improved tissue lesions, and promoted cancer cell apoptosis. Sin decreased the levels of inflammatory cytokines, AST and ALT, and decreased the numbers of erythrocytes, leukocytes and platelets. Simultaneously, the expressions of Ki-67, CD44, VEGF and CD31 were decreased in the Sin group. Furthermore, Sin decreased the Bcl-2, Cyclin D1, CDK4, CDK6 and Survivin levels, but increased Bax, Cleaved-caspase3/pro-caspase3, P21 and P27 levels. More importantly, the combination of Sin and Sor treatment was more effective than treatment alone.

Conclusion: A rat orthotopic liver carcinoma model was established under the guidance of B-ultrasound, and Sin had a therapeutic effect on orthotopic liver carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis* / drug effects
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Male
  • Morphinans* / pharmacology
  • Morphinans* / therapeutic use
  • Rats
  • Rats, Sprague-Dawley*
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use

Substances

  • sinomenine