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Deciphering the molecular mechanism of tetrandrine in inhibiting hepatocellular carcinoma and increasing sorafenib sensitivity by combining network pharmacology and experimental evaluation
- Source :
- Pharmaceutical Biology, Vol 60, Iss 1, Pp 75-86 (2022), Pharmaceutical Biology, article-version (VoR) Version of Record
- Publication Year :
- 2022
- Publisher :
- Taylor & Francis Group, 2022.
-
Abstract
- Context The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. Objective Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. Materials and methods CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. Results For SMMC7721 (IC50 = 22.5 μM) and PLC8024 (IC50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). Discussion and conclusions TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.
- Subjects :
- Male
Carcinoma, Hepatocellular
Mice, Nude
Pharmaceutical Science
RM1-950
Network Pharmacology
Benzylisoquinolines
liver cancer
Inhibitory Concentration 50
Mice
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Drug Discovery
Animals
Humans
Cell Proliferation
Pharmacology
Mice, Inbred BALB C
TOR Serine-Threonine Kinases
Liver Neoplasms
apoptosis
General Medicine
Sorafenib
Xenograft Model Antitumor Assays
chemosensitivity
Complementary and alternative medicine
pi3k/akt signalling
Drug Resistance, Neoplasm
traditional chinese medicine
Disease Progression
Molecular Medicine
cell cycle
Therapeutics. Pharmacology
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
systematic pharmacology
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 17445116 and 13880209
- Volume :
- 60
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Biology
- Accession number :
- edsair.doi.dedup.....1e1569c2c57ba9e667923a39b10efe75