Crocin Combined with Cisplatin Regulates Proliferation, Apoptosis, and EMT of Gastric Cancer Cells via the FGFR3/MAPK/ERK Pathway In vitro and In vivo .

Autor: Li Y; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China., Guo QJ; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China.; High Altitude Medicine Research Center, Key Laboratory of High Altitude Medicine, Ministry of Education Qinghai-Utah Joint Research Key Lab for High Altitude Medicine Qinghai University, XiNing, Qinghai, 810001, China., Chen R; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China., Zhao L; High Altitude Medicine Research Center, Key Laboratory of High Altitude Medicine, Ministry of Education Qinghai-Utah Joint Research Key Lab for High Altitude Medicine Qinghai University, XiNing, Qinghai, 810001, China., Cui X; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China., Deng Y; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China., Luo YS; Department of Oncology, Affiliated Hospital of Qinghai University, XiNing, Qinghai, China.; High Altitude Medicine Research Center, Key Laboratory of High Altitude Medicine, Ministry of Education Qinghai-Utah Joint Research Key Lab for High Altitude Medicine Qinghai University, XiNing, Qinghai, 810001, China.
Jazyk: angličtina
Zdroj: Current cancer drug targets [Curr Cancer Drug Targets] 2024; Vol. 24 (8), pp. 835-845.
DOI: 10.2174/1568009624666230915111239
Abstrakt: Introduction: Cisplatin (DDP)-based chemotherapy remains the main therapeutic strategy for human gastric cancer (GC). Combination therapy with Chinese medicine monomers and DDP has been investigated as a means to enhance the anti-tumor effect of DDP while reducing toxicity.
Material and Methods: Previous studies have shown that crocin combined with DDP can inhibit the apoptosis of BG-823 GC cells. However, the mechanism of this combination therapy in inhibiting GC is not fully unclear. In this study, we measured the IC 50 values of crocin combined with DDP in AGS cells and assessed its effect on cell proliferation using an MTT assay. Furthermore, we assessed apoptosis, cell migration, and EMT-related protein levels by using flow cytometry, scratch assay, and Western blotting, respectively. Our results showed that crocin combined with DDP inhibited the proliferation, induced apoptosis, and inhibited invasion and EMT. Next, we performed RNA sequence and KEGG enrichment analysis on GC cells treated with Crocin+DDP.
Results: The results showed that the most significant factor down-regulated by this combination therapy was Fibroblast growth factor receptor 3 (FGFR3) expression and that a differential gene was enriched in the MAPK/ERK pathway. We further constructed an FGFR3 OE transfection plasmid to overexpress FGFR3 and evaluate its effects on proliferation, apoptosis, migration, EMT, and MAPK/ERK pathway proteins in GC cells. We also conducted subcutaneous tumorigenesis experiments in nude mice to evaluate the effects of crocin and DDP on the progression of GC xenografts in vivo . Finally, we performed a rescue experiment using the MAPK/ERK pathway inhibitor PD184352.
Conclusion: Our results showed that up-regulation of FGFR3 reversed the inhibitory effect of crocin+DDP on the MAPK/ERK signaling pathway. Still, this effect could be counteracted by PD184352, which simultaneously regulated the proliferation, apoptosis, and EMT of AGS cells. In conclusion, crocin, combined with DDP, inhibits proliferation, apoptosis, and EMT of GC through the FRFR3/MAPK/ERK pathway.
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Databáze: MEDLINE
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