Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycl...Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly （P〈0.05） inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly （P〈0.05） changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 （T14）. Meanwhile, YSY-01A could inhibit the TNF-a-induced NF-kB nuclear translocation and lead to the increase of 1kBa as well as the decrease of IKK and Gadd45a In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.展开更多
Signal transducer and activator of transcription 3（STAT3） is a dual functional transcription factor with the functions of signal transduction and transcription regulation. It is reported that the expression of STAT3...Signal transducer and activator of transcription 3（STAT3） is a dual functional transcription factor with the functions of signal transduction and transcription regulation. It is reported that the expression of STAT3 in ovarian cancer is significantly higher and STAT3 can facilitate ovarian cancer growth and metastasis. To clarify the definite effect and molecular mechanism of STAT3 involved in ovarian cancer growth and metastasis, STAT3 expression was significantly downregulated by transfecting ovarian cancer model SK-OV-3 cells with the plasmid vector which express specific RNAi that targets human STAT3. The downregulated STAT3 not only decreased the invasion and migration but also inhibited the proliferation of SK-OV-3 cells. Western blot assay shows that the expression of vascular endothelial growth factor（VEGF） and that of Survivin were reduced in the cells with the plasma vector expressing specific RNAi that targets human STAT3. These results demonstrate that STAT3 involved in the invasion and migration of SK-OV-3 regulates the expression of VEGF and Survivin. In addition, VEGF and Survivin could play an important role in ovarian cancer growth and metastasis.展开更多
Objective: Cinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of giant toads and is utilized in traditional Chinese medicine (Chan Su). CINO has been used as a ca...Objective: Cinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of giant toads and is utilized in traditional Chinese medicine (Chan Su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Recently, CINO has been shown to inhibit lung cancer cell function and has been implicated in several other disease processes. In this study, we pursued the potential anticancer application of CINO using the ovarian tumor cell line SK-OV-3. Study Design: We evaluated the effect of CINO on cultures of SK-OV-3. Cells were treated with 0.1, 0.5, 1, 5, and 10 μM CINO. Cell proliferation, migration, invasion, and viability were measured using commercially available kits. Cell cycle progression was evaluated by a Cell Cycle Phase Determination Kit. Apoptosis was evaluated by an Apoptotic Blebs Assay Kit;cell cycle arrest and apoptotic signaling were determined by fluorescence-activated cell sorting (FACS) analysis. Results: CINO at ≥ 0.5 μM inhibited SKOV-3 cell proliferation, migration, and invasion (p < 0.05). There was a higher (p < 0.05) percentage of S phase cells in groups treated with CINO at 0.5 μM. CINO at ≥ 0.5 μM down regulated expression of Proliferating Cell Nuclear Antigen (PCNA) and caused cell death. Conclusion: This data demonstrates that CINO impairs SK-OV-3 cell function via cell cycle arrest and apoptotic signaling, suggesting CINO be further investigated as a novel anti-ovarian cancer agent.展开更多
基金Eleventh Five-Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930-010)National Science Foundation of China(Grant No.81172915)a grant from Major New Drugs Research and Development Platform of Peking University(Grant No.2009ZX09301-010)
文摘Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly （P〈0.05） inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly （P〈0.05） changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 （T14）. Meanwhile, YSY-01A could inhibit the TNF-a-induced NF-kB nuclear translocation and lead to the increase of 1kBa as well as the decrease of IKK and Gadd45a In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.
基金Supported by the Basis of Bethune Medical Research Fund of Jilin Province of China(No.200705114)
文摘Signal transducer and activator of transcription 3（STAT3） is a dual functional transcription factor with the functions of signal transduction and transcription regulation. It is reported that the expression of STAT3 in ovarian cancer is significantly higher and STAT3 can facilitate ovarian cancer growth and metastasis. To clarify the definite effect and molecular mechanism of STAT3 involved in ovarian cancer growth and metastasis, STAT3 expression was significantly downregulated by transfecting ovarian cancer model SK-OV-3 cells with the plasmid vector which express specific RNAi that targets human STAT3. The downregulated STAT3 not only decreased the invasion and migration but also inhibited the proliferation of SK-OV-3 cells. Western blot assay shows that the expression of vascular endothelial growth factor（VEGF） and that of Survivin were reduced in the cells with the plasma vector expressing specific RNAi that targets human STAT3. These results demonstrate that STAT3 involved in the invasion and migration of SK-OV-3 regulates the expression of VEGF and Survivin. In addition, VEGF and Survivin could play an important role in ovarian cancer growth and metastasis.
文摘Objective: Cinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of giant toads and is utilized in traditional Chinese medicine (Chan Su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Recently, CINO has been shown to inhibit lung cancer cell function and has been implicated in several other disease processes. In this study, we pursued the potential anticancer application of CINO using the ovarian tumor cell line SK-OV-3. Study Design: We evaluated the effect of CINO on cultures of SK-OV-3. Cells were treated with 0.1, 0.5, 1, 5, and 10 μM CINO. Cell proliferation, migration, invasion, and viability were measured using commercially available kits. Cell cycle progression was evaluated by a Cell Cycle Phase Determination Kit. Apoptosis was evaluated by an Apoptotic Blebs Assay Kit;cell cycle arrest and apoptotic signaling were determined by fluorescence-activated cell sorting (FACS) analysis. Results: CINO at ≥ 0.5 μM inhibited SKOV-3 cell proliferation, migration, and invasion (p < 0.05). There was a higher (p < 0.05) percentage of S phase cells in groups treated with CINO at 0.5 μM. CINO at ≥ 0.5 μM down regulated expression of Proliferating Cell Nuclear Antigen (PCNA) and caused cell death. Conclusion: This data demonstrates that CINO impairs SK-OV-3 cell function via cell cycle arrest and apoptotic signaling, suggesting CINO be further investigated as a novel anti-ovarian cancer agent.
