Nowadays, most studies focused on cancer stem cells (CSCs) through their abilities to cause tumorigenicity, drug resistance, and cancer recurrence. On the other side, nonsteroidal anti-inflammatory drugs (NSAIDs) have been taken into consideration because of cheapness and availability. For the reasons mentioned above, we have studied the effect of ibuprofen as an NSAID on CSCs derived from AGS and MKN-45 gastric cancer cell lines to perform effective cancer therapy. We evaluated cell viability, spheroid body formation, monolayer, and soft agar colony formation to express the anti-cancer effect of ibuprofen on CSCs. Also, real-time RT-PCR data of stemness markers and genes affected on, or downstream of Wnt signaling pathway were evaluated. Our findings suggest that ibuprofen at 1,000 μM for 48 h can reduce cell proliferation, stemness features in CSCs by changing the expression level of CD44, OCT3/4, SOX2, Nanog, and KLF4 as stemness markers. Furthermore, ibuprofen can have an inhibitory role in Wnt signaling pathway by changing the expression level of some genes, including CTNNB1, CTNNBIP1, SMARCD1, PYGO2, SUFU, CASK, and KREMEN1. According to our study, ibuprofen has an anti-proliferative effect on CSCs derived from AGS and MKN-45 cells.

Despite the fact that much research has focused on gastric cancer, it is still a worldwide concern, because of the difficulties with factors such as signaling pathway crosstalk and gastric cancer stem cell (GCSC). Placental growth factor (PlGF) is one of these factors, and its tumorigenicity potential still remains a question. As a result, we have investigated the effect of PlGF knockdown on apoptosis and genes involved in the Wnt signaling pathway, and apoptosis in cancer stem cells derived from AGS an MKN-45 gastric cancer cell lines. We isolated GCSCs from MKN-45 and AGS cell lines on a nonadherent surface. Then the cell viability, the real-time reverse transcription-polymerase chain reaction data of the genes involved in the Wnt signaling pathway, and apoptosis were evaluated. Furthermore, DNA laddering was used to show the apoptotic effect and DNA fragmentation caused by the PlGF knockdown. Our investigation revealed that the PlGF knockdown with PlGF-specific small interfering RNA at 40 pmol for GCSCs derived from MKN-45 and AGS at 24 hours can significantly affect the cell viability, the Wnt signaling pathway, and the apoptosis-related genes expression. In conclusion, we showed the PlGF knockdown may induce apoptosis via the Wnt signaling pathway in GCSCs.

No abstract

Background: Gastric cancer is a daunting global problem with unsatisfactory treatment. Due to the key role of Gastric Cancer Stem-like Cells (GCSCs) in all stages of gastric cancer and the failure of contemporary anticancer therapies, many research efforts are focusing on these treatment-resistant cells. Pantoprazole, as recently considered antitumor agent with well-documented effects on tumorigenesis inhibition, has seldom been investigated in GCSCs in previous studies. We aimed to study the influence of pantoprazole on cell proliferation, apoptosis and on the transcription of genes involved in the cell proliferation and apoptosis pathways. Materials and methods: Herein, we isolated GCSCs from MKN-45 cell line, on a non-adherent surface and then evaluated the effect of pantoprazole on cell growth and apoptosis of GCSCs by means of MTT, DNA laddering and quantitative real-time RT-PCR techniques. Results: Our findings showed that treated cells with pantoprazole decreased cell proliferation and induced apoptosis. PCNA (Proliferating Cell Nuclear Antigen) and antiapoptotic Bcl2 genes were downregulated and Bax and CASP3 proapoptotic genes, as well as tumor suppressor p53 gene were overexpressed. Conclusion: Conclusion: Our results revealed that pantoprazole induced apoptosis and declined tumor growth and support the idea that pantoprazole played as a promising break-through in gastric cancer therapy.