SPARC enhances 5-FU chemosensitivity in gastric cancer by modulating epithelial-mesenchymal transition and apoptosis

• Published in: Biochemical and biophysical research communications Vol. 558; pp. 134 - 140
• Main Authors: Ma, Ju, Ma, Yongchen, Chen, Shanwen, Guo, Shihao, Hu, Jianwen, Yue, Taohua, Zhang, Junling, Zhu, Jing, Wang, Pengyuan, Chen, Guowei, Liu, Yucun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.06.2021
• Subjects: actin; angiogenesis; Apoptosis; cell movement; cell proliferation; cell viability; Chemosensitivity; cysteine; cytoskeleton; EMT; fluorouracil; Gastric cancer; humans; neoplasm cells; plasmids; protein secretion; SPARC; stomach neoplasms; transfection; Chemosensitivity; SPARC; Gastric cancer; EMT; Apoptosis
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2021.04.009

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. •SPARC overexpression induced gastric cancer cell lines more sensitive to 5-FU treatment.•SPARC inhibited the EMT process in gastric cancer cells by downregulating the expression level of EMT-associated proteins and F-actin.•Overexpression of SPARC could promote the apoptosis of gastric cancer cells treated by 5-FU through activating the PARP/caspase-3 pathway.•SPARC overexpression significantly increased the chemosensitivity of the gastric cancer cell line to 5-FU in vivo.