ABSTRACT
Objective To investigate the effect of the Notch signaling pathway on the proliferation and invasion of human SW982 synovial sarcoma cells. Methods SW982 cells and normal human synovial cells were routinely cultured, and the expression of proteins related to the Notch pathway was compared. The Notch signaling pathway was manipulated by NICD1 overexpression, CFB1 shRNA lentivirus, and the γ-secretase inhibitor, DAPT. CCK-8 and wound healing assays were carried out to investigate the role of the Notch signaling pathway in SW982 cells. Results The Notch signaling pathway clearly showed higher activity in human SW982 synovial sarcoma cells than in normal human synovial cells (P ＜ 0.05). The proliferation and invasion of SW982 cells were significantly upregulated by overexpressing NICD1; however, were suppressed by downregulating the Notch signaling pathway using CFB1 shRNA or DAPT (P ＜ 0.05). Conclusion Our findings demonstrate that the proliferation and invasion of human SW982 synovial sarcoma cells are dependent on Notch signaling pathway activity.
ABSTRACT
Objective: To explore the molecular mechanisms of the anticancer activities of penicilazaphilone C against gastric cancer. Methods: In vitro effects of penicilazaphilone C on cell growth, proliferation, and apoptosis were evaluated by MTT, BrdU, MTS, colony formation assays, Hoechst 33258 staining, and flow cytometry. Related proteins were examined by Western blotting assays. The expression of Notch receptor was analyzed using real-time PCR. In vivo antitumor activities of penicilazaphilone C were observed in nude mice. Results: Compared to the controls, penicilazaphilone C suppressed cell proliferation and promoted apoptosis in MGC-803 and SGC-7901 cells. The Notch/PTEN/AKT axis was involved in the activating penicilazaphilone C-induced apoptosis. Penicilazaphilone C decreased levels of Notch, NICD, phospho-PTEN and phospho- AKT compared to controls. The penicilazaphilone C-induced inhibition of Notch-related protein expression levels and the resulting apoptosis could be reversed by overexpression of Notch1 or/and Notch2. Moreover, penicilazaphilone C inhibited tumor growth in mice bearing tumours derived from MGC-803 and SGC-7901 cells, respectively. Conclusions: Penicilazaphilone C can induce the apoptosis by suppressing the activation of the proteolytic cleavage of the Notch receptor and subsequently blocking the PTEN/AKT signaling axis in gastric cancer cells. Thus, penicilazaphilone C is a potential alternative agent for the treatment of gastric cancer.