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Xiaotan sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells

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World Journal of Gastroenterology 2014年第36期20卷 13105-13118页

作者： Bing Yan Long Liu Ying Zhao Li-Juan Xiu Da-Zhi Sun Xuan Liu Ye Lu Jun Shi Yin-Cheng Zhang Yong-Jin Li Xiao-Wei Wang Yu-Qi Zhou Shou-Han Feng Can Lv Pin-Kang Wei Zhi-Feng Qin Department of Traditional Chinese Medicine Changzheng Hospital the Second Military Medical University Department of Traditional Chinese Medicine Changhai Hospital the Second Military Medical University

AIM: To determine the underlying mechanisms of action and influence of Xiaotan sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor(VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells(GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44+ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth(GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density(MVD)(GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium-(82.87% ± 6.53%) and high-dose XTSJ groups(77.43% ± 7.34%) was detected at 24 h in the CD44+ GCSCs group compared with the saline group(95.42% ± 5.76%) and the low-dose XTSJ group(90.74% ± 6.57%)(P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44- groups; significant differences were only detected in the high-dose XTSJ group at 48 h(78.57% ± 6.94%) and 72 h(72.12% ± 7.68%) when compared with the other CD44- groups(P

关键词： Gastric cancer stem-like cells Xiaotan sanjie deco

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Xiaotan sanjie decoction inhibits interleukin-8-induced metastatic potency in gastric cancer

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World Journal of Gastroenterology 2015年第5期21卷 1479-1487页

作者： Jun Shi Pin-Kang Wei Department of Traditional Chinese Medicine Shanghai Changzheng HospitalThe Second Military Medical University

AIM:To investigate the interaction between Xiaotan sanjie(XTSJ) decoction and interleukin-8(IL-8) and its effect on adhesion,migration and invasion of SGC-7901 gastric cancer cells.METHODS:SGC-7901 gastric cancer cells were exposed to serum containing XTSJ decoction and/orIL-8(1 ng/m L).SGC-7901 cell adhesion to fibronectin,an extracellular matrix component,was detected using the Cell Counting Kit-8.Migration and invasion abilities of SGC-7901 cells were detected by scratch wound and Transwell chamber assays.Then,protein(immunofluorescence and Western blot) and m RNA levels(quantitative polymerase chain reaction) of cluster of differentiation 44(CD44),a cell adhesion molecule,were measured in 72-h-cultured SGC-7901 cells.RESULTS:Cell adhesion was promoted by IL-8(P = 0.001),but was inhibited by XTSJ decoction(P = 0.0001).Similarly,IL-8 promoted SGC-7901 cell invasion(P = 0.003),and XTSJ decoction inhibited cell invasion(P = 0.001).IL-8 induced SGC-7901 cell migration,but this was inhibited by XTSJ decoction.IL-8 up-regulated CD44 protein(P = 0.028) and m RNA expression(P = 0.002),whereas XTSJ decoction inhibited CD44 protein expression(P = 0.0001),but not m RNA expression(P = 0.275).An interaction between XTSJ decoction and IL-8 was confirmed in the invasion(P = 0.001) and CD44 m RNA expression of SGC-7901 cells(P = 0.010),but not in cell adhesion(P = 0.051).CONCLUSION:XTSJ decoction may inhibit adhesion,migration and invasion of gastric cancer cells,which is partly associated with down-regulation of IL-8.

关键词： Xiaotan sanjie decoction Interleukin-8 Migration A

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Effective ingredients, potential targets and mechanism in cancers treatment of Bushen Jiedu sanjie recipe

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TMR Cancer 2019年第1期2卷 133-142页

作者： Ru Jia Xue-Qing Hu Yan Wang Li-Hong Zhou Hua Sui Qi Li Qing Ji Department of Medical Oncology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Cancer Institute Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China

Objective: To analyze the active compounds, potential drug targets and corresponding therapy cancer of Bushen Jiedu sanjie Recipe (BSJDSJR) based on network pharmacology and bioinformatics technology. Methods: The network databases including Cancer HSP, TCMSP, TCMID, TCM-PTD, TCM Database@Taiwan and DrugBank were applied to screen the active compounds, potential drug targets and corresponding cancers of BSJDSJR. Cytoscape3.3 software was used to construct the network between active compounds of Chinese medicine and the corresponding targets. Then, the enrichment of biological processes and KEGG pathways of BSJDSJR were analyzed using DAVID database. Results: According to Oral bioavailability (OB)≥30% and drug like index (DL)≥0.18, 129 active compounds in BSJDSJR were screened out and they targeted to 301 proteins. These targets were closely associated with the occurrence of various cancers, such as bladder cancer, pancreatic cancer, non-small cell lung cancer and colorectal cancer. Further investigation showed that, there were lots of active compounds in BSJDSJR are closely connected with the COX-2/β-catenin signaling pathway, STAT3 signaling pathway and MAPK/ERK signaling pathway. Conclusions: Based on the network pharmacology, the study disclosed the active chemical compounds, potential targets and possible action cancers of BSJDSJR.

关键词： Bushen Jiedu sanjie Recipe Network pharmacology Active compound Drug target Cancer Molecular mechanism

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