Abstract: OBJECTIVE: To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription — Qingyihuaji formula(QYHJ) — from Traditional Chinese Medicine(TCM).METHODS: Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups: Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine.Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors(Notch-1, Notch-2,Notch-3, and Notch-4) and their Jagged ligands(Jagged-1 and Jagged-2) in dissected tumor tissuewere detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells(CSCs), to evaluate the impact of QYHJ extract on pancreatic CSCs.RESULTS: QYHJ extract treatment effectively inhibited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups(P < 0.05), while gemcitabine alone had no significant effect in down-regulating Jagged-1(P > 0.05).No significant difference was observed in the expression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group(P > 0.05). Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment(P < 0.05), and the combined treatment was more effective than gemcitabine alone(P < 0.05).CONCLUSION: The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.

Key words: Pancreatic neoplasms, Stem cells, Notch4 protein,mouse, Serrate proteins, Qingyihuaji formula