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Pterostilbene enhances sorafenib’s anticancer effects on gastric adenocarcinoma
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Sorafenib has been approved for the treatment of certain cancers in clinic. However, the effects of sorafenib on gastric adenocarcinoma (GAC) were still limited. This study aimed to evaluate both in vitro and in vivo efficacy of sorafenib in combination with pterostilbene (PTE) on the treatment of GAC. Here, the morphological changes and cell viability were recorded in both N87 and MKN45 cells. The cell cycle profile and apoptosis were assessed by flow cytometry. Subcutaneous tumour xenografts were constructed in nude mice, and IHC staining of the dissected tumour tissues was conducted. Our results showed that PTE enhanced sorafenib's inhibitory effects on cell viability. The obvious down‐regulation of cyclin D1, Cdk‐2, Cdk‐4, Cdk‐6 and p62 and the up‐regulation of LC3II, caspase‐9, caspase‐3 and PARP cleavages were observed for the combination treatment with PTE and sorafenib than monotherapy. The combination treatment resulted in a higher level of cell cycle arrest at G1 phase and apoptosis than either drug. Besides, drug combination significantly enhanced the inhibition of tumour growth than sorafenib or PET alone in nude mice. The percentage of Ki‐67‐ and PCNA‐positive cells was distinctly reduced, and the apoptotic cells was obviously increased when compared with single drug therapy. Altogether, PET obviously enhanced sorafenib's antitumour effects against GAC through inhibiting cell proliferation, inducing autophagy and promoting apoptosis. The combination therapy with PET and sorafenib may serve as a novel therapeutic strategy for treating GAC and deserve further clinical trials.
- Subjects :
- Male
0301 basic medicine
Sorafenib
pterostilbene
Pterostilbene
Combination therapy
Cell Survival
Mice, Nude
Antineoplastic Agents
Apoptosis
Adenocarcinoma
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
synergistic effect
Stomach Neoplasms
In vivo
Cell Line, Tumor
Stilbenes
Autophagy
Animals
Medicine
Viability assay
Cell Shape
gastric adenocarcinoma (GAC)
neoplasms
Mice, Inbred BALB C
combination chemotherapy
Cell Death
business.industry
Cell growth
Drug Synergism
Combination chemotherapy
Original Articles
Cell Biology
Cell cycle
G1 Phase Cell Cycle Checkpoints
Xenograft Model Antitumor Assays
digestive system diseases
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Original Article
business
medicine.drug
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....9ce2d96cc701c4067abff08c3019b769