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SPARC enhances 5-FU chemosensitivity in gastric cancer by modulating epithelial-mesenchymal transition and apoptosis
- Source :
- Biochemical and Biophysical Research Communications. 558:134-140
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.
- Subjects :
- 0301 basic medicine
Epithelial-Mesenchymal Transition
Cell
Biophysics
Mice, Nude
Antineoplastic Agents
Apoptosis
Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Stomach Neoplasms
Cell Line, Tumor
medicine
Animals
Humans
Osteonectin
Viability assay
Epithelial–mesenchymal transition
RNA, Small Interfering
Molecular Biology
Mice, Inbred BALB C
Caspase 3
Chemistry
Cell growth
Cell migration
Cell Biology
Transfection
Xenograft Model Antitumor Assays
Actins
Up-Regulation
030104 developmental biology
medicine.anatomical_structure
Drug Resistance, Neoplasm
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Female
Fluorouracil
Poly(ADP-ribose) Polymerases
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 558
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....589bd1b33fc6b6c92c45e482ba59cb81