Effect of Zengmian Yiliu Formula and Its Effective Components on Notch/Jagged1 Signaling Pathway of Ovarian Cancer Stem Cell Transplanted Tumor in Nude Mice
10.13422/j.cnki.syfjx.20201522
- VernacularTitle:增免抑瘤方及有效组分对卵巢癌干细胞裸鼠移植瘤Notch/Jagged1信号通路的影响
- Author:
Jie ZHANG
1
;
Cheng-cheng LIANG
2
;
Ai-zhong YANG
2
;
Cong QI
3
Author Information
1. Longhua Hospital，Shanghai University of Traditional Chinese Medicine（TCM），Shanghai 200032，China
2. Graduate School，Shanghai University of TCM，Shanghai 200120，China
3. Shuguang Hospital，Shanghai University of TCM，Shanghai 200120，China
- Publication Type:Research Article
- Keywords:
Zengmian Yiliu formula;
effective components;
nude mice;
ovarian cancer stem cells;
Notch/Jagged1
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(15):46-53
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of Zengmian Yiliu （ZMYL） formula and its effective components （PAWU） on the growth inhibition of ovarian cancer stem cell transplanted tumor in nude mice and the Notch signal receptor （Notch） / Notch signal ligand 1 （Jagged1） signal pathway in tumor tissue. Method:Ovarian cancer stem cells were cultured in serum-free suspension to establish the transplanted tumor model of ovarian cancer stem cells in nude mice， and then divided into model group， ZMYL group （36 g·kg-1）， PAWU group （5.8 g·kg-1）， cisplatin （DDP） group （2.5 g·kg-1）， and PAWU （5.8 g·kg-1） + DDP group （2.5 mg·kg-1）.After successful modeling， the drugs were given by gavage for 21 days.To observe the effect of Zengmian Yiliu decoction and its effective components on tumor weight in nude mice， the morphological changes of tumor cells were observed under light microscope， immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were used to detect the expressions of Notch 1， Jagged1， Hairy and enhancer of split 1 （Hes1） protein and mRNA in tumor tissues. Result:The tumor inhibition rates of ZMYL， PAWU， DDP and combination groups were 35.91%， 32.94%， 57.65% and 69.05%， respectively.Compared with the model group， the tumor weight of ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with PAWU group， the tumor weight of combination groups decreased significantly （P<0.05）.Immunohistochemistry showed that compared with the model group， the positive expressions of Notch1， Jagged1 in ZMYL group， PAWU group， DDP group and combination groups were down-regulated （P<0.05），and the positive expressions of Hes1 in ZMYL group， DDP group and combination groups were down-regulated （P<0.05）.Compared with combination groups， the positive expressions of Notch1， Jagged1 and Hes1 in ZMYL group， PAWU group， DDP group were up-regulated （P<0.05）. Real time PCR showed that compared with the model group， the expressions of Notch1 mRNA in ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with model group， the expressions of Jagged1 and Hes1 mRNA in ZMYL group， PAWU group and combination groups decreased significantly （P<0.05）.Compared with DDP group， the expressions of Notch1， Jagged1 and Hes1 mRNA in combination groups decreased significantly （P<0.05）. Conclusion:The growth of ovarian cancer stem cells transplanted in nude mice can be inhibited by Zengmian Yiliu formula and its effective components.The effective components have a significant synergistic effect in the combination with cisplatin.Its mechanism is correlated to the inhibition of Notch/Jagged1 signaling pathway activation.
