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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 Tongfu granules contribute to the prevention of stress ulcers

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World Journal of Gastroenterology 2013年第33期19卷 5473-5484页

作者： Bing Yan Jun Shi Li-Juan Xiu Xuan Liu Yu-Qi Zhou Shou-Han Feng Can Lv Xiu-Xia Yuan Yin-Cheng Zhang Yong-Jin Li Pin-Kang Wei Zhi-Feng Qin Department of Traditional Chinese Medicine Changzheng HospitalSecond Military Medical University

AIM:To investigate the efficacy and potential mechanism of xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statistically significant differences

关键词： Stress ulcer xiaotan Tongfu granule Inflammation Heat shock protein 70 Proliferation and apoptosis Gastric emptying rate

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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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