1.Preliminary study of Realgar and arsenic trioxide on gut microbiota of mice.
Yu-Ting SUN ; Huan-Hua XU ; Yao NIE ; Yu-Guang WANG ; Zeng-Chun MA ; Wei ZHOU ; Hong-Ling TAN ; Yue GAO
China Journal of Chinese Materia Medica 2020;45(1):142-148
The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.
Animals
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Arsenic Trioxide/pharmacology*
;
Arsenicals/pharmacology*
;
Bacteria/drug effects*
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Gastrointestinal Microbiome/drug effects*
;
Mice
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Sulfides/pharmacology*
2.Effects of vitamin C combined with arsenic trioxide on the apoptosis of Hep-2 cell.
Weimin XU ; Chenghua SHU ; Jin HU ; Yuhua YE
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(4):171-173
OBJECTIVE:
To study synergistic effect of Vitamin C (VitC) combined with arsenic trioxide (As2 O3)-on human laryngocarcinoma Hep-2 cell line apoptosis.
METHOD:
Human laryngocarcinoma cell line Hep-2 was cultured in vitro, and incubated with As2 O3 or jointly with VitC. The inhibition ability of Hep-2 cells was determined by methyl thiazolyl tetrazolium (MTT) assay, while the apoptosis was mensurated by the flow cytometry with Annexin-V/PI.
RESULT:
Compared with the use of As2 O3 separately, the combination of As2 O3 and VitC could increase the inhibition ability and the apoptosis rate of Hep-2 cells markedly (P < 0.05).
CONCLUSION
Combination of As2 O3 with VitC could markedly increase arsenic trioxide (As2 O3)-induced apoptosis of Hep-2 cells.
Apoptosis
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drug effects
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Arsenic Trioxide
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Arsenicals
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pharmacology
;
Ascorbic Acid
;
pharmacology
;
Cell Line, Tumor
;
Drug Synergism
;
Humans
;
Oxides
;
pharmacology
3.Effect of arsenic trioxide combined with adriamycin on the proliferation and apoptosis of human lymphoma cells.
Ranxin HUANG ; Xiaolin LI ; Xiaochun HUANG ; Xiaogang YANG ; Wenqi LI
Journal of Central South University(Medical Sciences) 2009;34(6):515-522
OBJECTIVE:
To determine the effect of arsenic trioxide combined with adriamycin(ADM) on the proliferation and apoptosis of human lymphoma cells.
METHODS:
Raji cells were divided into an experimental group and a control group, and the experimental group was further divided into 1 micromol/L As(2)O(3) group,2 micromol/L As(2)O(3) group, ADM group,1 micromol/L As(2)O(3) and ADM group,2 micromol/L As(2)O(3) and ADM group. Human lymphoma cells Raji were treated with As(2)O(3) combined with ADM. Wright-Giemsa dying assay was used to observe the apoptosis morphology of lymphoma cells. The proliferation of the cells treated with As(2)O(3) and adriamycin was detected by the method of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT). Flow cytometry(FCM) was used to detect the apoptosis rate of lymphoma and the fluorescene density in the lymphocytes. Effect of arsenic trioxide and adriamycin on the mutant p53 expression in Raji cells was detected by semi-quantitive RT-PCR.
RESULTS:
Evident apoptotic morphological changes of Raji cells were observed 24 hours after treatment with As(2)O(3) or ADM. Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the inhibition ratio significantly (P<0.05), and the inhibition rate was related to the concentration and action time of As(2)O(3) (P<0.05). Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the apoptosis rate of lymphoma cells with obvious difference (P<0.05). Semi-quantitive and RT-PCR showed that the expression of mutant p53 in As(2)O(3) and ADM alone and combined groups was obviously less than that in the control (P<0.05). After the treatment with 1 micromol/L and 2 micromol/L As(2)O(3), the fluorescene density in the Raji cells was 18.53 and 18.12, 0.056 and 0.023 times increase respectively.There was no difference (P>0.05).
CONCLUSION
As(2)O(3) and ADM alone or combined can inhibit the proliferation, induce cell apoptosis, and downregulate the expression of mutant p53 in vitro. As(2)O(3) combined with ADM has synergistic anti-lymphoma cell effect in vitro. As(2)O(3) has no significant effect on the concentration of ADM on the Raji cells, but can enhance the chemosensitivity of Raji cells, and its mechanism may be that it can downregulate the expression of mutant p53.
Antineoplastic Agents
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pharmacology
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Apoptosis
;
drug effects
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Arsenic Trioxide
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Arsenicals
;
pharmacology
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Cell Line, Tumor
;
Cell Proliferation
;
drug effects
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Doxorubicin
;
pharmacology
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Drug Synergism
;
Humans
;
Lymphoma
;
pathology
;
Oxides
;
pharmacology
4.Effects of arsenic trioxide combined with cisplatin on the growth of human nasopharyngeal carcinoma cells and reversion of RASSF1A hympermethylation.
Xueqin HUANG ; Xiaogang WANG ; Junli HU ; Hui ZHOU ; Yuefei ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(14):1061-1065
OBJECTIVE:
To investigate the effect of arsenic trioxide (As2O3) combined with cisplatin on expression of RASSF1A in nude mice with human nasopharyngeal carcinoma xenograft.
METHOD:
The models of human poorly differentiated nasopharyngeal carcinoma in nude mice were established and randomly divided into four groups, control group (NaCl group), As2O3 group, DDP group and As2O3 + DDP group. The expression of RASSF1A mRNA and protein were detected by Real-time RT-PCR and immunohistochemistry respectively. The methylation rate of RASSF1A promoter CpG islands was analyzed by HRM.
RESULTS:
Experimental groups could obviously inhibit the growth of tumor and up-regulate the expression of RASSF1A. The methylation rate of RASSF1A in transplanted tumors in experimental groups was lower than the control group. Especially As2O3 combined with DDP were superior to the single drug use.
CONCLUSION
As2O3 inhibits the growth of human nasopharyngeal carcinoma cell strain CNE2 xenograft in nude mice and increases mRNA expression of RASSF1A. As2O3 inhibits the malignant phenotypes of human nasopharyngeal carcinoma cells and reverses hypermethylation of RASSF1A.
Animals
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Arsenic Trioxide
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Arsenicals
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pharmacology
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Carcinoma
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Cell Line, Tumor
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Cisplatin
;
pharmacology
;
DNA Methylation
;
drug effects
;
Humans
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Mice
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Mice, Nude
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Nasopharyngeal Carcinoma
;
Nasopharyngeal Neoplasms
;
genetics
;
pathology
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Neoplasm Transplantation
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Oxides
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pharmacology
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Tumor Suppressor Proteins
;
genetics
;
Xenograft Model Antitumor Assays
5.Arsenic trioxide induced apoptosis in retinoblastoma cells in vitro and its possible mechanism.
Yun LI ; Luo-Sheng TANG ; Hong-Wei SHEN
Journal of Central South University(Medical Sciences) 2008;33(6):476-480
OBJECTIVE:
To explore the effect of arsenic trioxide on the apoptosis of retinoblastoma cell line HXO-RB(44) and the possible mechanism.
METHODS:
The effect of arsenic trioxide on the proliferation of retinoblastoma cell line HXO-RB(44) was observed by MTT colorimetric assay; the apoptosis of the HXO-RB(44) was examined by AO/EB staining and flow cytometry analysis (Annexin V+ PI staining); caspase-3 activity and bcl-2/bax expression in the HXO-RB(44) were detected by cpp32 colorimetric assay kit and Western blot.
RESULTS:
Arsenic trioxide inhibited the proliferation of HXO-RB(44) cell in dose and duration-dependent manner in vitro; arsenic trioxide significantly increased the apoptosis in HXO-RB(44) cells. The activation of caspase-3 was increased, and the rate of bcl-2/bax was down-regulated in the HXO-RB(44) cells processed with arsenic trioxide.
CONCLUSION
Arsenic trioxide can inhibit the proliferation of retinoblastoma cell HXO-RB(44) in vitro by apoptosis induction. The apoptosis induction is possibly related to the caspase-3 activation and bcl-2/bax down-regulation.
Antineoplastic Agents
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pharmacology
;
Apoptosis
;
drug effects
;
Arsenic Trioxide
;
Arsenicals
;
pharmacology
;
Caspase 3
;
biosynthesis
;
Humans
;
Oxides
;
pharmacology
;
Proto-Oncogene Proteins c-bcl-2
;
biosynthesis
;
Retinal Neoplasms
;
pathology
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Retinoblastoma
;
pathology
;
Tumor Cells, Cultured
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bcl-2-Associated X Protein
;
biosynthesis
6.CircRNA-0028171 regulates arsenic trioxide-induced apoptosis in vascular endothelial cells.
Ji-Chen WU ; Sai-Di JIN ; Jia-Hang SONG ; Xin-Qi LIU ; Wen-Jun MA ; Lin CHANG ; Xiao-Xiang GUAN ; Ming-Yu ZHANG ; Jia-Qi LIU ; Hui FU ; Ying WANG ; Chao-Qian XU
Acta Physiologica Sinica 2022;74(5):763-772
The present study was aimed to investigate the effects of circRNA-0028171 on the apoptosis of vascular endothelial cells induced by arsenic trioxide (As2O3). Human umbilical vein endothelial cells (HUVECs) were treated with 0-15 μmol/L As2O3 for 24 h. Then, cellular viability was measured by MTT assay. The expression levels of circRNA-0028171, Bcl-2 and Bax mRNA were detected by real-time quantitative PCR. Bcl-2/Bax protein ratio was detected by Western blot. Whether circRNA-0028171 was involved in the regulation of HUVECs by As2O3 was investigated by transfection with overexpression plasmid of circRNA-0028171 and siRNA. The results showed that compared with the control group, As2O3 group showed decreased cellular viability, reduced Bcl-2/Bax mRNA and protein ratios, and significantly lower expression of circRNA-0028171. Overexpression of circRNA-0028171 inhibited apoptosis of HUVECs induced by As2O3. Knockdown of circRNA-0028171 by siRNA promoted As2O3-induced apoptosis in HUVECs. These results suggest that circRNA-0028171 is involved in the vascular endothelial cell apoptosis induced by As2O3.
Humans
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Arsenic Trioxide/pharmacology*
;
RNA, Circular
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bcl-2-Associated X Protein/metabolism*
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RNA, Small Interfering/metabolism*
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Apoptosis
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Proto-Oncogene Proteins c-bcl-2/metabolism*
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Human Umbilical Vein Endothelial Cells/metabolism*
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RNA, Messenger/metabolism*
7.Inhibitory effect of arsenic trioxide combined with cisplatin on human nasopharyngeal carcinoma xenograft and DAPK in nude mice.
Xueqin HUANG ; Xiaogang WANG ; Junli HU ; Hui ZHOU ; Keyuan ZHOU ; Yuefei ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(9):479-483
OBJECTIVE:
To study the inhibitory effect of Arsenic Trioxide (As2O3) combined with diamminedichloroplatinum (DDP) on the growth of human nasopharyngeal carcinoma cell strain CNE-2Z xenograft in nude mice, and to explore the possible effect mechanisms of the antitumor.
METHOD:
The models of human poorly differentiated nasopharyngeal carcinoma in nude mice were established and randomly divided into four groups, control group, As2O3 group, DDP group and As2O3 + DDP group. The effect of antitumor on each group was studied. The specimen obtained from the mice were detected by optical microscope and tdt-mediated dutp rock end labeling (tunel) method. Expression of DAPK was detected by real time-PCR and immunohistochemistry.
RESULT:
As2O3 group and AS2O3 + DDP group could obviously inhibit the growth of tumor, induce the apoptosis of human naso pharyngeal carcinoma cell and up-regulate the expression of RASSF1A.
CONCLUSION
As2O3 can greatly inhibit the growth of human nasopharyngeal carcinoma cell strain CNE-2Z xenograft in nude mice, which were related to the induced apoptosis of human nasopharyngeal carcinoma cell and up-regulated expression of DAPK Combination of As2O3 with DDP seem to be more effective.
Animals
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Apoptosis
;
drug effects
;
Arsenic Trioxide
;
Arsenicals
;
administration & dosage
;
pharmacology
;
Carcinoma
;
Cell Line, Tumor
;
Cisplatin
;
administration & dosage
;
pharmacology
;
Death-Associated Protein Kinases
;
metabolism
;
Gene Expression Regulation, Neoplastic
;
Humans
;
Mice
;
Mice, Nude
;
Nasopharyngeal Carcinoma
;
Nasopharyngeal Neoplasms
;
metabolism
;
pathology
;
Oxides
;
administration & dosage
;
pharmacology
;
Xenograft Model Antitumor Assays