Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated wi...Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated with As2O3 in different concen- trations （1, 2, 4 and 8 pM）, for 24, 48 and 72 h, respectively, and cell proliferation was tested by MTT assay. Apoptosis was observed with electron microscope and DNA electrophoresis. The distribution of cell cycles and cell apoptosis were detected by flow cytometry. Expression of the Survivin gene was determined by real-time quantitative RT-PCR. Results： As2O3 （1-8 μM） inhibited Raji cells growth effectively in a dose- and time-dependent manner. As2O3 at 2-8μM could induce cell apoptosis and cell cycle arrest. However, As2O3（1 μM） inhibited Raji proliferation only by cell cycle arrest, without any symptoms of cell apoptosis. At the same time, Survivin gene expression was down-regulated after the treatment. Conclusion： As2O3 could induce substantial proliferation inhibition, cell cycle arrest and apoptosis in Raji cell. Cell cycle arrest might be a reason why apoptosis occurs. As2O3 can markedly down-regulate expression of the Survivin gene in a dose- and timedependent manner. The down-regulated Survivin gene might be leading to cell apoptosis by As2O3.展开更多
Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages...Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.展开更多
基金a grand from the Educational Committee Scientific Research Foundation of Yunnan Province. (No. 06z095c).
文摘Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated with As2O3 in different concen- trations （1, 2, 4 and 8 pM）, for 24, 48 and 72 h, respectively, and cell proliferation was tested by MTT assay. Apoptosis was observed with electron microscope and DNA electrophoresis. The distribution of cell cycles and cell apoptosis were detected by flow cytometry. Expression of the Survivin gene was determined by real-time quantitative RT-PCR. Results： As2O3 （1-8 μM） inhibited Raji cells growth effectively in a dose- and time-dependent manner. As2O3 at 2-8μM could induce cell apoptosis and cell cycle arrest. However, As2O3（1 μM） inhibited Raji proliferation only by cell cycle arrest, without any symptoms of cell apoptosis. At the same time, Survivin gene expression was down-regulated after the treatment. Conclusion： As2O3 could induce substantial proliferation inhibition, cell cycle arrest and apoptosis in Raji cell. Cell cycle arrest might be a reason why apoptosis occurs. As2O3 can markedly down-regulate expression of the Survivin gene in a dose- and timedependent manner. The down-regulated Survivin gene might be leading to cell apoptosis by As2O3.
基金supported by the National Science Foundation for Excellent Young Scholars(China)(No.32122052)the National Natural Science Foundation Regional Innovation and Development(China)(No.U19A2003).
文摘Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.
