Anti-tumor effect of the extract from qingyihuaji formula on pancreatic cancer by down-regulating Notch-4 and Jagged-1.

Abstract

OBJECTIVE:

To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription--Qingyi-huaji 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 tissue were 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 ex- pression 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.

• Authors: Yanli Xu, Feiye Zhu, Shan Xu, Luming Liu
• Journal: Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan (J Tradit Chin Med) Vol. 35 Issue 1 Pg. 77-83 (Feb 2015) ISSN: 0255-2922 [Print] China
• PMID: 25842732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Calcium-Binding Proteins
• Drugs, Chinese Herbal
• Intercellular Signaling Peptides and Proteins
• JAG1 protein, human
• Jag1 protein, mouse
• Jagged-1 Protein
• Membrane Proteins
• Proto-Oncogene Proteins
• Qingyihuaji
• Receptor, Notch4
• Receptors, Notch
• Serrate-Jagged Proteins
• Notch4 protein, mouse

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Calcium-Binding Proteins (genetics, metabolism)
• Down-Regulation (drug effects)
• Drugs, Chinese Herbal (administration & dosage)
• Female
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Jagged-1 Protein
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Nude
• Pancreatic Neoplasms (drug therapy, genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• Receptor, Notch4
• Receptors, Notch (genetics, metabolism)
• Serrate-Jagged Proteins
• Signal Transduction (drug effects)