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...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-I, 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 inhib- ited 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.展开更多
Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are re...Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.展开更多
基金Supported by the National Natural Science Foundation of China(No.81173461)China Scholarship Council(No.201306100055)
文摘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-I, 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 inhib- ited 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.
文摘Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.
