Time filter

Source Type

Qian L.,Wujiang No 1 Peoples Hospital | Qian L.,Shanghai University | Liu Y.,Wujiang No 1 Peoples Hospital | Xu Y.,Shanghai University | And 5 more authors.
Cancer Letters | Year: 2015

Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment. © 2015 Elsevier Ireland Ltd.


Xu Y.,Shanghai University | Peng Z.,Shanghai University | Ji W.,Shanghai University | Li X.,Shanghai University | And 7 more authors.
BioMed Research International | Year: 2015

Activation of hepatic stellate cells (HSCs) is a critical event in process of hepatic fibrogenesis and cirrhosis. Matrine, the active ingredient of Sophora, had been used for clinical treatment of acute/chronic liver disease. However, its potency was low. We prepared a high potency and low toxicity matrine derivate, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities on antihepatic fibrosis. This study demonstrated that WM130 results in a decreased proliferative activity of HSC-T6 cells, with the half inhibitory concentration (IC50) of 68 M. WM130 can inhibit the migration and induce apoptosis in HSC-T6 cells at both concentrations of 68 M (IC50) and 34 M (half IC50). The expression of SMA, Collagen I, Collagen III, and TGF-β1 could be downregulated, and the protein phosphorylation levels of EGFR, AKT, ERK, Smad, and Raf (p-EGFR, p-AKT, p-ERK, p-Smad, and p-Raf) were also decreased by WM130. On the DMN-induced rat liver fibrosis model, WM130 can effectively reduce the TGF-β1, AKT, SMA, and p-ERK levels, decrease the extracellular matrix (ECM) formation, and inhibit rat liver fibrosis progression. In conclusion, this study demonstrated that WM130 can significantly inhibit the activation of HSC-T6 cells and block the rat liver fibrosis progression by inducing apoptosis, suppressing the deposition of ECM, and inhibiting TGF-β/Smad and Ras/ERK pathways. © 2015 Yang Xu et al.


PubMed | No 105 Hospital Of Pla, Shanghai University, Wujiang No 1 Peoples Hospital and Second Military Medical University
Type: Journal Article | Journal: Cancer letters | Year: 2015

Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment.


Liu Y.,Wujiang No 1 Peoples Hospital | Bi T.,Wujiang No 1 Peoples Hospital | Dai W.,Wujiang No 1 Peoples Hospital | Wang G.,Wujiang No 1 Peoples Hospital | And 3 more authors.
Tumor Biology | Year: 2015

Oxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has long been employed clinically to treat cancers. Here, we investigated the synergistic effect of OMT with 5-fluorouracil (5-Fu) on the tumor growth inhibition of hepatocellular carcinoma cells (HCC; Hep-G2 and SMMC-7721) and explored the underlying mechanism. Cells were treated with OMT and/or 5-Fu and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay, and immunohistochemistry. OMT and 5-Fu inhibited the proliferation of Hep-G2 and SMMC-7721 cells, and combination treatment with OMT and 5-Fu resulted in a combination index <1, indicating a synergistic effect. Co-treatment with OMT and 5-Fu caused G0/G1 phase arrest by upregulating P21 and P27 and downregulating cyclin D, and induced apoptosis through increasing the production of reactive oxygen species (ROS) and decreasing the levels of p-ERK. In addition, the inhibition of ROS respectively reversed the cell death induced by 5-Fu + OMT, suggesting the key roles of ROS in the process. More importantly, 5-Fu and OMT in combination exhibit much superior tumor weight and volume inhibition on SMMC-7721 xenograft mouse model in comparison to 5-Fu or OMT alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which was consistent with our in vitro results. Taken together, our findings indicated that OMT sensitizes HCC to 5-Fu treatment by the suppression of ERK activation through the overproduction of ROS, and combination treatment with OMT and 5-Fu would be a promising therapeutic strategy for HCC treatment. © 2015 International Society of Oncology and BioMarkers (ISOBM)


Liu Y.,Wujiang No 1 Peoples Hospital | Bi T.,Wujiang No 1 Peoples Hospital | Dai W.,Wujiang No 1 Peoples Hospital | Wang G.,Wujiang No 1 Peoples Hospital | And 3 more authors.
Technology in Cancer Research and Treatment | Year: 2015

Oxymatrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess anticancer activities in vitro and in vivo. However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of oxymatrine in human hepatoma cells (Hep-G2 and SMMC-7721) in vitro and in vivo. Hep-G2 and SMMC-7721 cells were treated by oxymatrine and subjected to methyl thiazolyl tetrazolium analysis, Hoechst 33342 staining, annexin V/propidium iodide double staining, reverse transcription polymerase chain reaction, and Western blot analysis. In addition, SMMC-7721 xenograft tumors were established in male nude BALB/c mice, and oxymatrine was intravenously administered to evaluate the anticancer capacity in vivo. Our results showed that oxymatrine inhibited the proliferation and induced apoptosis of Hep-G2 and SMMC-7721 cells in a dose-dependent manner in vitro. Furthermore, the RNA and protein expression of Bax and caspase 3 levels were significantly upregulated, whereas the expression of Bcl-2 was downregulated. These protein interactions may play a pivotal role in the regulation of proliferation and apoptosis. More importantly, our in vivo studies showed that administration of oxymatrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated an increase of Bax and caspase 3 and a decrease of Bcl-2 in tumor tissues following oxymatrine treatment which are consistent with the in vitro results. Taken together, our findings indicated that oxymatrine can inhibit cell proliferation and induce apoptosis of human hepatoma Hep-G2 and SMMC-7721 cells and might offer a therapeutic potential advantage for human hepatoma chemoprevention or chemotherapy. © 2015, © The Author(s) 2015.


PubMed | Wujiang No 1 Peoples Hospital
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

Oxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has long been employed clinically to treat cancers. Here, we investigated the synergistic effect of OMT with 5-fluorouracil (5-Fu) on the tumor growth inhibition of hepatocellular carcinoma cells (HCC; Hep-G2 and SMMC-7721) and explored the underlying mechanism. Cells were treated with OMT and/or 5-Fu and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay, and immunohistochemistry. OMT and 5-Fu inhibited the proliferation of Hep-G2 and SMMC-7721 cells, and combination treatment with OMT and 5-Fu resulted in a combination index <1, indicating a synergistic effect. Co-treatment with OMT and 5-Fu caused G0/G1 phase arrest by upregulating P21 and P27 and downregulating cyclin D, and induced apoptosis through increasing the production of reactive oxygen species (ROS) and decreasing the levels of p-ERK. In addition, the inhibition of ROS respectively reversed the cell death induced by 5-Fu+OMT, suggesting the key roles of ROS in the process. More importantly, 5-Fu and OMT in combination exhibit much superior tumor weight and volume inhibition on SMMC-7721 xenograft mouse model in comparison to 5-Fu or OMT alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which was consistent with our in vitro results. Taken together, our findings indicated that OMT sensitizes HCC to 5-Fu treatment by the suppression of ERK activation through the overproduction of ROS, and combination treatment with OMT and 5-Fu would be a promising therapeutic strategy for HCC treatment.


PubMed | Wujiang No 1 Peoples Hospital
Type: Journal Article | Journal: Naunyn-Schmiedeberg's archives of pharmacology | Year: 2016

Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects in vitro and in vivo. Here, we investigated the anti-cancer efficacy and adjuvant chemotherapy action of lupeol in gastric cancer (GC) cells (SGC7901 and BGC823) and explored the underlying mechanisms. Cells were treated with lupeol and/or 5-fluorouracil (5-Fu) and subjected to cell viability, colony formation, apoptosis, western blot, semiquantitative RT-PCR, and xenograft tumorigenicity assay. Our results showed that lupeol and 5-Fu inhibited the proliferation of SGC7901 and BGC823 cells, and combination treatment with lupeol and 5-Fu resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with lupeol and 5-Fu induced apoptosis through up-regulating the expressions of Bax and p53 and down-regulating the expressions of survivin and Bcl-2. Furthermore, co-treatment displayed more efficient inhibition of tumor weight and volume on BGC823 xenograft mouse model than single-agent treatment with 5-Fu or lupeol. Taken together, our findings highlight that lupeol sensitizes GC to 5-Fu treatment, and combination treatment with lupeol and 5-Fu would be a promising therapeutic strategy for human GC treatment.


PubMed | Wujiang No 1 Peoples Hospital
Type: Journal Article | Journal: Technology in cancer research & treatment | Year: 2016

Oxymatrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess anticancer activities in vitro and in vivo However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of oxymatrine in human hepatoma cells (Hep-G2 and SMMC-7721) in vitro and in vivo Hep-G2 and SMMC-7721 cells were treated by oxymatrine and subjected to methyl thiazolyl tetrazolium analysis, Hoechst 33342 staining, annexin V/propidium iodide double staining, reverse transcription polymerase chain reaction, and Western blot analysis. In addition, SMMC-7721 xenograft tumors were established in male nude BALB/c mice, and oxymatrine was intravenously administered to evaluate the anticancer capacity in vivo Our results showed that oxymatrine inhibited the proliferation and induced apoptosis of Hep-G2 and SMMC-7721 cells in a dose-dependent manner in vitro Furthermore, the RNA and protein expression of Bax and caspase 3 levels were significantly upregulated, whereas the expression of Bcl-2 was downregulated. These protein interactions may play a pivotal role in the regulation of proliferation and apoptosis. More importantly, our in vivo studies showed that administration of oxymatrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated an increase of Bax and caspase 3 and a decrease of Bcl-2 in tumor tissues following oxymatrine treatment which are consistent with the in vitro results. Taken together, our findings indicated that oxymatrine can inhibit cell proliferation and induce apoptosis of human hepatoma Hep-G2 and SMMC-7721 cells and might offer a therapeutic potential advantage for human hepatoma chemoprevention or chemotherapy.

Loading Wujiang No 1 Peoples Hospital collaborators
Loading Wujiang No 1 Peoples Hospital collaborators