RESUMEN
BACKGROUND: Pancreatic cancer is a highly malignant tumor of the gastrointestinal system whose emerging resistance to chemotherapy has necessitated the development of novel antitumor treatments. Scoparone, a traditional Chinese medicine monomer with a wide range of pharmacological properties, has attracted considerable attention for its antitumor activity. AIM: To explore the potential antitumor effect of scoparone on pancreatic cancer and the possible molecular mechanism of action. METHODS: The target genes of scoparone were determined using both the bioinformatics and multiplatform analyses. The effect of scoparone on pancreatic cancer cell proliferation, migration, invasion, cell cycle, and apoptosis was detected in vitro. The expression of hub genes was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the molecular mechanism was analyzed using Western blot. The in vivo effect of scoparone on pancreatic cancer cell proliferation was detected using a xenograft tumor model in nude mice as well as immunohistochemistry. RESULTS: The hub genes involved in the suppression of pancreatic cancer by scoparone were obtained by network bioinformatics analyses using publicly available databases and platforms, including SwissTargetPrediction, STITCH, GeneCards, CTD, STRING, WebGestalt, Cytoscape, and Gepia; AKT1 was confirmed using qRT-PCR to be the hub gene. Cell Counting Kit-8 assay revealed that the viability of Capan-2 and SW1990 cells was significantly reduced by scoparone treatment exhibiting IC50 values of 225.2 µmol/L and 209.1 µmol/L, respectively. Wound healing and transwell assays showed that scoparone inhibited the migration and invasion of pancreatic cancer cells. Additionally, flow cytometry confirmed that scoparone caused cell cycle arrest and induced apoptosis. Scoparone also increased the expression levels of Bax and cleaved caspase-3, decreased the levels of MMP9 and Bcl-2, and suppressed the phosphorylation of Akt without affecting total PI3K and Akt. Moreover, compared with the control group, xenograft tumors, in the 200 µmol/L scoparone treatment group, were smaller in volume and lighter in weight, and the percentages of Ki65- and PCNA-positive cells were decreased. CONCLUSION: Our findings indicate that scoparone inhibits pancreatic cancer cell proliferation in vitro and in vivo, inhibits migration and invasion, and induces cycle arrest and apoptosis in vitro through the PI3K/Akt signaling pathway.
RESUMEN
There has been an increase in morbidity and mortality related to coronary heart disease (CHD) in China in recent years. Numerous clinical experiences and studies have shown that traditional Chinese medicine (TCM) plays an important role in the prevention, treatment, and prognosis of CHD. However, the mechanism of TCM in the treatment of CHD has not yet been elucidated. The circRNA-miRNA-mRNA network consists of miRNA that is competitively bound by circRNA, and miRNA regulates the transcription level of mRNA. Through literature review, we found that the circRNA-miRNA-mRNA network acts to contribute to certain effects to CHD such as myocardial hypertrophy, myocardial fibrosis, and heart failure. TCM contains constituents that act against CHD by antiatherosclerosis and apoptosis inhibition action, cardiac and cardiomyocyte protection, and these components also promote cell growth and protection of the vascular system by regulating miRNAs. Therefore, we consider that the circRNA-miRNA-mRNA network may be a new regulatory mechanism for the effective treatment of CHD by TCM.