[Nano-vesicles derived from M1 macrophages affect the development of mouse endometriosis by polarizing M2 macrophages to M1 phenotype].

Objective To explore whether nano-vesicles derived from M1 macrophages (M1-NVs) can reprogram M2 macrophages into M1 phenotype and further affect the development of endometriosis (EMS). Methods Extracellular vesicles (EVs) were isolated from macrophage culture supernatant by differential centrifugation. Immunofluorescence cytochemistry was used to detect the expression of vimentin, CD31 and F4/80 to identify endometrial stromal cells (EMS-ESCs), HUVECs and polarized peritoneal macrophages of EMS patients. M1-NVs were prepared by filtering cell suspension through (5, 1, 0.4, 0.22)µm polycarbonate membrane filters after syringe aspiration at 0-4 DegreesCelsius. Flow cytometry was used to analyze the polarization of RAW264.7 mouse peritoneal macrophages in vitro, and reverse transcription PCR (RT-qPCR) was employed to detect mRNA expression of VEGF, CD86, interleukin-6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), arginase 1 (Arg1), CD163, CD206, and IL-10. PKH67-labeled M1-NVs were co-cultured with EMS-ESCs, HUVECs and macrophages. And tubule formation experiments were conducted to assess the impact of M1-NVs on the tubule formation of HUVECs. TranswellTM invasion and migration assays were employed to evaluate changes in the migration and invasion abilities of EMS-ESCs. Results By monitoring the contents of NVs, it was found that NVs contained much more protein and other bioactive particles than the same amount of EVs; immunofluorescence staining results showed that PKH67 labeled M1-NVs were internalized by EMS-ESCs, HUVECs and macrophages when co-cultured. The results of flow cytometry and RT-qPCR multi-target analysis showed that after treatment with different concentrations of M1-NVs or M0-NVs, 20 µg/mL of M1-NVs could effectively reprogram M2 macrophages into M1 macrophages compared with M0-NVs. TransewellTM results showed that compared with the blank group and M0-NVs group, the number of EMS-ESCs migrating from the upper chamber to the lower chamber after M1-NV treatment was significantly reduced, while the number of EMS-ESCs treated with M2NVs increased significantly. The invasion situation was similar to the migration situation, indicating that M1-NVs directly or indirectly inhibited invasion, migration and tubule formation of EMS-ESCs in vitro. Conclusion M1-NVs reprogrammes M2 macrophages into M1 macrophages by internalization of primary cells and macrophages, thereby inhibiting invasion, migration and angiogenesis of EMS-ESCs, and further hindering the occurrence and development of EMS.

[Bioinformatics analysis of the association between long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and immune cell infiltration in ovarian serous cystadenocarcinoma].

Objective To investigate the expression of long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and its relationship with immune infiltration in ovarian serous cystadenocarcinoma (OSC), and to determine its prognostic role in OSC. Methods The Cancer Genome Atlas (TCGA) database was utilized to retrieve the expression of USP30-AS1 and clinical information of 384 OSC patients. Wilcoxon rank-sum test was employed to compare the expression of USP30-AS1 between OSC and normal ovarian tissues. Logistic regression analysis was conducted to assess the relationship between clinical pathological features and USP30-AS1. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate enrichment pathways and functions and quantify the degree of immune cell infiltration in USP30-AS1. Based on the expression level of long non-coding RNA (lncRNA) USP30-AS1, the samples were divided into high and low expression groups according to the expression mean. Log-rank tests, univariate and multivariate proportional hazards model (Cox) were used to compare prognostic differences between different USP30-AS1 expression groups. The impact of lncRNA USP30-AS1 expression on other genomic analyses was also analyzed. Results High expression of USP30-AS1 was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) stage of the tumor. Multivariate survival analysis indicated that USP30-AS1 expression level served as an independent prognostic marker for OSC. GSEA data showed that high expression of USP30-AS1 might activate programmed death 1 (PD-1) signaling pathway, cytotoxic T lymphocyte-associated protein 4 (CTLA4) pathway, B-cell receptor signaling pathway, cell apoptosis, fibroblast growth factor receptor (FGFR) signaling pathway, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. The expression of USP30-AS1 was negatively correlated with immune cell infiltration, including B cells, CD4+ T cells, dendritic cells, CD8+ T cells, and neutrophils. Conclusion USP30-AS1 may be used as a prognostic molecular marker for OSC.

Ultrahigh Energy-Storage Density of BaTiO3-Based Ceramics via the Interfacial Polarization Strategy.

Lead-free dielectric capacitors are excellent candidates for pulsed power devices. However, their low breakdown strength (Eb) strongly limits their energy-storage performance. In this study, Sr0.7Bi0.2TiO3 (SBT) and Bi(Mg0.5Hf0.5)O3 (BMH) were introduced into BaTiO3 (BT) ceramics to suppress interfacial polarization and modulate the microstructure. The results show that the introduction of SBT and BMH increases the band gap width, reduces the domain size, and, most importantly, successfully attenuates the interfacial polarization. Significantly enhanced Eb values were obtained in (1 - x)(0.65BaTiO3-0.35Sr0.7Bi0.2TiO3)-xBi(Mg0.5Hf0.5)O3 (BSBT-xBMH) ceramics. Meanwhile, the interfacial polarization was reduced to near zero in the sample with x = 0.10, achieving an ultrahigh Eb (64 kV/mm) and a very large recoverable energy-storage density (Wrec ≈ 9.13 J/cm3). In addition, the sample has excellent thermal stability (in line with EIA-X7R standards) and frequency stability. These properties indicate that the BSBT-0.10BMH ceramic holds promising potential for the application of pulsed power devices.

Determination of Potential Therapeutic Targets and Prognostic Markers of Ovarian Cancer by Bioinformatics Analysis.

This study is to study the expression of CXCRs in ovarian cancer tissues and their value in prognosis. The expressions of CXCR1-CXCR7 mRNA between ovarian tumor tissues and normal tissues and in different pathological types of ovarian tumor tissues were compared by ONCOMINE online tool. The relationship between the expression of CXCRs and clinical pathological staging was studied by GEPIA. Kaplan-Meier plotter online tool was used to analyze prognosis. Finally, GO and KEGG analyses and protein interaction network analysis were performed for CXCRs by the DAVID software to predict their function, and cBioPortal was used to identify the key functional genes. The expression of CXCR3/4/7 mRNA in ovarian cancer tissues was higher than that in normal ovarian tissues, and the expression of CXCR4 was the highest (fold change = 306.413, P < 0.05). The expression of CXCR1/2/3/4/7 mRNA in different pathological types of ovarian tumors was significantly different (P < 0.05). Only CXCR5 expression level was associated with tumor staging. Survival analysis showed that high CXCR7 mRNA expression and low CXCR5/6 expression were associated with the shortening of overall survival. High CXCR4/7 expression and low CXCR5/6 expression were associated with the shortening of progression-free survival. High CXCR2/4 expression and low CXCR5/6 expression were closely related to the shortening of postprogressing survival. Protein interaction network analysis showed that GNB1, PTK2, MAPK1, PIK3CA, GNB4, GNA11, KNG1, and ARNT proteins were closely related to the CXC receptor family. CXCR3/4/7 are potential therapeutic targets, and CXCR2/4/5/6/7 are new markers for the prognosis of ovarian cancer.

Roles of Non-Coding RNAs in Cervical Cancer Metastasis.

Metastasis remains to be a huge challenge in cancer therapy. The mechanism underlying cervical cancer metastasis is not well understood and needs to be elucidated. Recent studies have highlighted the diverse roles of non-coding RNAs in cancer progression and metastasis. Increasing numbers of miRNAs, lncRNAs and circRNAs are found to be dysregulated in cervical cancer, associated with metastasis. They have been shown to regulate metastasis through regulating metastasis-related genes, epithelial-mesenchymal transition, signaling pathways and interactions with tumor microenvironment. Moreover, miRNAs can interact with lncRNAs and circRNAs respectively during this complex process. Herein, we review literatures up to date involving non-coding RNAs in cervical cancer metastasis, mainly focus on the underlying mechanisms and highlight the interaction network between miRNAs and lncRNAs, as well as circRNAs. Finally, we discuss the therapeutic prospects.

miR-548e Sponged by ZFAS1 Regulates Metastasis and Cisplatin Resistance of OC by Targeting CXCR4 and let-7a/BCL-XL/S Signaling Axis.

Ovarian cancer (OC) is a severe malignancy featuring a poor prognosis due to rapid metastasis and chemotherapy resistance. In this study, we extensively investigated the upstream and downstream mechanisms of miR-548e in regulating OC progression and cisplatin resistance. Our results indicated that ZFAS1 was highly expressed and promoted OC cell proliferation, migration, invasion, and cisplatin resistance by directly suppressing miR-548e expression. ZFAS1 co-localized with miR-548e in the cytosols of OC cells. miR-548e repressed CXCR4 expression, and elevated CXCR4 expression promoted OC cell proliferation, migration, invasion, and cisplatin resistance. Cisplatin resistance induced by ZFAS1 and CXCR4 overexpression in OC cells was mediated by their suppression on let-7a and elevation of BCL-XL/S expression. ZFAS1 knockdown and miR-548e and let-7a overexpression impaired cisplatin resistance and suppressed lung metastatic nodule formation in nude mice. In conclusion, ZFAS1 binds with miR-548e to enhance CXCR4 expression to promote OC cell proliferation and metastasis, which also enhances cisplatin resistance by suppressing let-7a and elevating BCL-XL/S protein expression.

TiO2/(K,Na)NbO3 Nanocomposite for Boosting Humidity-Sensing Performances.

Nanomaterials of TiO2, (K0.5Na0.5)NbO3, and the TiO2/(K0.5Na0.5)NbO3 nanocomposite were successfully synthesized by a hydrothermal method. Impedance-type humidity sensors were fabricated based on these materials. Our results reveal that the impedance of the TiO2/(K0.5Na0.5)NbO3 sensor changes by 5 orders of magnitude with an ultrahigh sensing response of Sf = 166 470 recorded at 100 Hz in the tested relative humidity (RH) range of 12-94%. This value is almost 2 and 4 orders of magnitude larger than that of the (K0.5Na0.5)NbO3 and TiO2 sensors, respectively. Interestingly, satisfactory response/recovery time (25/38 s, within 5 min), very small hysteresis (<5%), excellent stability, and good repeatability were also achieved in the TiO2/(K0.5Na0.5)NbO3 sensor. The improved sensing properties are ascribed to the synergistic effect of TiO2/(K0.5Na0.5)NbO3 heterojunction, which contributes the impedance that is susceptible to environmental humidity. This work underscores that it is a facile way to boost humidity-sensing performance by constructing proper nanocomposites.

Dendritic cells aggregate inflammation in experimental osteoarthritis through a toll-like receptor (TLR)-dependent machinery response to challenges.

AIMS: Dendritic cells (DCs) and Toll-like receptor (TLR) participate in mediating inflammation process. However, the functional role of TLR expressed on DCs in osteoarthritis (OA) development has not been defined yet. The purpose of this study was to investigate the role and mechanism of TLR and DCs in the progression of experimental osteoarthritis (OA). MATERIALS AND METHODS: Experimental OA model was induced by iodoacetate injection. Expressions of toll-like receptors in DCs of OA mice were detected by qRT-PCR and flow cytometry. TLR agonists lipopolysaccharide (LPS) and R848 or TLR antagonist FP7 were used, and the levels of TLRs and inflammatory cytokines were examined by qRT-PCR and ELISA. KEY FINDINGS: The expression levels of TLR family members were increased in DCs derived from synovial fluid of OA mice compared with the sham mice. In vitro, OA mice-derived DCs had increased production of inflammatory cytokine after TLR agonists LPS and R848 challenge, while TLR challenges did not affect DCs maturation. Inhibition of TLR by TLR antagonist FP7 blocked TLR challenges-induced increased inflammation in DCs. In mice, administration of FP7 attenuated LPS-induced inflammatory response and OA condition. SIGNIFICANCE: Increased TLR expression in OA-derived DCs contributes to the inflammation condition and potentially acts as a therapeutic target for osteoarthritis.

Expression of MTA1 in endometriosis and its relationship to the recurrence.

Metastasis-associated gene 1 (MTA1) is correlated with prognosis of many tumors. However, little is known about the role of MAT1 in endometriosis and its relationship with the recurrence of endometriosis.The expression of MTA1 in normal, eutopic and ectopic endometrium was detected by immunohistochemistry and RT-PCR, respectively. The relationship of MTA1 expression with the recurrence of endometriosis was evaluated.In the normal endometrium, eutopic endometrium and ectopic endometrium, the positive rates of MTA1 expression showed a gradually increasing trend. In addition, the MTA1 expression difference between each two groups was significant (P < .0125). However, there was no significant difference between proliferative phase and secretory phase in each group (P > .05). In the ectopic endometrium, MTA1 expression in the severe phases (III-IV) was significantly higher than that in mild phases (I-II) (P < .05), indicating the expression of MTA1 correlates with r-AFS staging (P < .05). Additionally, the MTA1 mRNA level was also closely related to the stages of r-AFS, but not to the proliferative phase or secretory phase of endometrium. Logistic regression analysis showed that r-AFS stage and MTA1 overexpression were risk factors for the recurrence of endometriosis. While, postoperative pregnancy was a protective factor for its relapse.MTA1 is closely associated with the occurrence and development of Ems. Thus, MTA1 level may be used as a new indicator to predict the progression of endometriosis.

Impact of laparoscopy on the biological behavior and gene expression of endometrial adenocarcinoma cells.

The current study investigated the effect of laparoscopy on the biological behavior and gene expression of endometrial adenocarcinoma cells. Totally, 40 patients with stage I endometrial adenocarcinoma and 20 patients with benign uterine diseases were enrolled in this study. For patients with endometrial adenocarcinoma, laparoscopy was performed in 20 cases and laparotomy was carried out in the other 20 cases. Total laparoscopic hysterectomy was performed in patients with benign diseases. Cell apoptotic rate and the gene expression of N-myc, Fas, metastasis-associated protein 1 (MTA1), and nm23-H1 were determined in the normal and cancerous endometrial tissues both preoperatively and postoperatively. For endometrial adenocarcinoma cells, laparoscopy, instead of laparotomy, promoted the apoptosis of endometrial adenocarcinoma cells, down-regulated the expression of apoptosis suppressor gene N-myc and metastasis-promoting gene MTA1, up-regulated the expression of apoptosis-promoting gene Fas and metastasis suppressor gene nm23-H1. However, laparoscopy did not affect the apoptotic rate and gene expression in normal endometrial cells. Laparoscopy may be used as a safe and effective intervention for endometrial cancer.

Comparison of the Clinical Effectiveness of PFNA, PFLCP, and DHS in Treatment of Unstable Intertrochanteric Femoral Fracture.

In this study, a randomized trial was conducted to compare the clinical effectiveness of proximal femoral locking compression plate (PFLCP), dynamic hip screw (DHS), and proximal femoral nail antirotation (PFNA) for unstable intertrochanteric femoral fracture treatment. Ninety patients diagnosed with unstable intertrochanteric femoral fracture were enrolled in this study at the department of orthopedics at Linyi Second People's Hospital between May 2010 and May 2012. Fractures were classified according to Tronzo-Evans classification, and the patients were randomly divided into 3 groups, PFLCP, DHS, and PFNA, with 30 patients in each group. The length of incision, operative time, intraoperative blood loss, postoperative drainage, postoperative weight-bearing ambulation time, and duration of fracture union were significantly lower in patients who underwent PFNA and PFLCP compared to patients treated with DHS. Furthermore, when the same clinical parameters were used for comparison, the PFNA group showed markedly lower values compared with the PFLCP group. The total incidence of postoperative complications was significantly different among the PFNA, PFLCP, and DHS groups, with the PFNA group exhibiting markedly lower complication rates compared with PFLCP and DHS groups. However, PFLCP and DHS groups did not show significant differences in the incidence of postoperative complications. Notably, the Harris hip score of PFNA group was markedly higher than the DHS group. In conclusion, our results provide convincing evidence that PFNA may be the most effective internal fixation treatment of unstable intertrochanteric femoral fracture.

Evaluation of shoulder function in clavicular fracture patients after six surgical procedures based on a network meta-analysis.

Purpose Using a network meta-analysis approach, our study aims to develop a ranking of the six surgical procedures, that is, Plate, titanium elastic nail (TEN), tension band wire (TBW), hook plate (HP), reconstruction plate (RP) and Knowles pin, by comparing the post-surgery constant shoulder scores in patients with clavicular fracture (CF). Methods A comprehensive search of electronic scientific literature databases was performed to retrieve publications investigating surgical procedures in CF, with the stringent eligible criteria, and clinical experimental studies of high quality and relevance to our area of interest were selected for network meta-analysis. Statistical analyses were conducted using Stata 12.0. Results A total of 19 studies met our inclusion criteria were eventually enrolled into our network meta-analysis, representing 1164 patients who had undergone surgical procedures for CF (TEN group = 240; Plate group = 164; TBW group = 180; RP group = 168; HP group = 245; Knowles pin group = 167). The network meta-analysis results revealed that RP significantly improved constant shoulder score in patients with CF when compared with TEN, and the post-operative constant shoulder scores in patients with CF after Plate, TBW, HP, Knowles pin and TEN were similar with no statistically significant differences. The treatment relative ranking of predictive probabilities of constant shoulder scores in patients with CF after surgery revealed the surface under the cumulative ranking curves (SUCRA) value is the highest in RP. Conclusion The current network meta-analysis suggests that RP may be the optimum surgical treatment among six inventions for patients with CF, and it can improve the shoulder score of patients with CF. Implications for Rehabilitation RP improves shoulder joint function after surgical procedure. RP achieves stability with minimal complications after surgery. RP may be the optimum surgical treatment for rehabilitation of patients with CF.

[Expression of metastasis tumor-associated protein 2 in cervical squamous carcinoma and its relationship with prognosis].

OBJECTIVE: To investigate the expression of metastasis tumor-associated protein 2 (MTA2) in cervical squamous carcinoma and its relationship with prognosis.
 Methods: Immunohistochemistry and real-time PCR were performed to determine the expression and distribution of MTA2 mRNA and protein in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical squamous carcinomas tissues, then its relationship with clinical pathological factors and prognosis was analyzed.
 Results: The positive rate of MTA2 protein in normal cervical tissue, CIN and cervical squamous cell carcinomas tissues were 0, 30.0%, 73.4%, respectively. The positive rate was associated with international federation of gynecology and obstetrics (FIGO) stage and lymph node metastasis, whereas there was no correlation with the age of patients or the degree of tumor differentiation. The expression of MTA2 mRNA in normal cervical tissue, CIN and cervical squamous carcinomas tissues was 0.437±0.028, 0.737±0.102 and 1.172±0.068, respectively. The positive rate was associated with FIGO stage and lymph node metastasis, whereas there was no correlation with the age of patients or the degree of tumor differentiation. The result of survival analysis showed poor overall survival time in the patients with high expression of MTA2. Multivariate COX proportional hazards model showed that the positive expression of MTA2 protein, FIGO stage and the metastasis of lymph node were independent prognostic factors for unfavorable clinical outcome of cervical cancer.
 Conclusion: The positive expression of MTA2 was closely related to the development, invasion and metastasis of cervical squamous cell carcinomas. The positive expression of MTA2 protein, FIGO stage and the metastasis of lymph node were independent prognostic factors for unfavorable clinical outcome of cervical cancer. The expression of MTA2 could be used as a potential molecular marker in evaluating the prognosis of cervical squamous cell carcinomas.

Laparoscopic surgery inhibits the proliferation and metastasis of cervical cancer cells.

AIMS: The present study is to investigate the effect of laparoscopic surgery on the proliferation and metastasis of cervical cancer cells. METHODS: A total of 40 patients with phase I squamous cell carcinoma of the cervix were enrolled in the study, and divided evenly into laparoscopic surgery group and laparotomy group. In addition, another 20 patients with benign uterine lesions received laparoscopic panhysterectomy using celoscopes and were enrolled as control group. Cell apoptotic rates were determined using flow cytometry. The expression of N-myc, Fas, metastasis-associated gene 1, and nm23-H1 genes in tissues were measured using quantitative real-time polymerase chain reaction. RESULTS: Cervical cancer cell apoptosis was promoted by laparoscopic surgery, but not affected by laparotomy. The expression of apoptosis suppressor gene N-myc in cervical cancer cells was reduced by laparoscopic surgery, but not affected by laparotomy. In addition, the expression of apoptosis promoting gene Fas in cervical cancer cells was enhanced by laparoscopic surgery, but not affected by laparotomy. Similarly, the expression of metastasis promoting gene MTA1 in cervical cancer cells was lowered by laparoscopic surgery, but not affected by laparotomy. Moreover, the expression of metastasis suppressor gene nm23-H1 in cervical cancer cells was increased by laparoscopic surgery, but not affected by laparotomy. Of note, laparoscopic panhysterectomy had no effect on the apoptosis or the expression of N-myc, Fas, MTA1 and nm23-H1 genes in normal cervical cells. CONCLUSIONS: Laparoscopic surgery is a safe treatment method for cervical cancer. It inhibits the proliferation and metastasis of cancer cells, but has no such effects on normal cells.

[Primary study of arsenic trioxide inhibits abdomino-metastatic tumor formation of human ovarian carcinoma in nude mice and its mechanisms].

BACKGROUND AND OBJECTIVE: Arsenic trioxide (As2O3) has been successfully used to treat the patients with acute promyelocyutic leukemia in clinic, and for the experimental studies of liver cancer, colorectal cancer, gastric cancer, etc. The objective of this study was to explore the inhibitory effect of As2O3 on the abdomino-metastasis of human ovarian carcinoma in nude mice and its mechanisms. METHODS: Compared with cisplatin(cDDP), the growth inhibiting rates to human ovarian cancer cell line 3AO by treatment with various concentrations of As2O3 for 48 h were determined by methyl thiazolyl tetrazolium(MTT) method. After implanted with 3AO cells 4 x 10(6) into abdominal cavity for 96 h, the nude mice were randomly divided into 5 groups and treated by intraperitoneal injection of normal saline, cisplatin, or different concentrations of As2O3. The rate of tumor formation, death rate, and survival period of tumor-bearing nude mice were evaluated. After treatment with As2O3, the changes of Fas, FasL, and nm23 gene expressions were estimated by flow cytometry (FCM). RESULTS: Compared with cisplatin, 3AO cell growth inhibiting rates by As2O3 were different significantly in concentration-dependent manner (P < 0.05); Compared with cisplatin, As2O3 could reduce the 3AO cell tumor formation rate in nude mice and the death rate of tumor-bearing nude mice, and prolong the survival period of tumor-bearing nude mice significantly (P < 0.05). As2O3 up-regulated Fas and nm23 gene expressions of abdominal cavity implanted tumors (P < 0.05), but did not affect FasL gene expression (P > 0.05). CONCLUSION: As2O3 could inhibit the abdomino-plantation of human ovarian carcinoma in nude mice and its mechanism may be associated with Fas gene and nm23 gene over-expressions.

[Apoptosis of drug-resistant human ovarian carcinoma cell line 3AO/cDDP induced by arsenic trioxide and its mechanism].

OBJECTIVE: To explore the effects of arsenic trioxide (As(2)O(3)) on the growth of drug-resistant human epithelial ovarian carcinoma cell line 3AO/cDDP and its possible mechanism. METHODS: Human epithelial ovarian carcinoma cell line 3AO and drug- resistant human epithelial ovarian carcinoma cell line 3AO/cDDP were cultured As(2)O(3) of different concentrations was added into the media. Cell culture without addition of As(2)O(3) was used as control. The growth inhibiting rates of 3AO/cDDP cells with various concentrations of As(2)O(3) in different time course (24, 48, 72, and 96 hours after) were studied by methyl thiazolyl tetrazolium (MTT) method. The apoptosis percentage, cell cycle phase distribution and expression of Fas/FasL gene were estimated by flow cytometry (FCM). The apoptosis phenotype of 3AO/cDDP cells was observed by cytoskeleton dying, and the apoptosis phenotype of 3AO cells was observed by acridine dying under fluorescent microscopy. RESULTS: 3AO/cDDP cell growing inhibiting rates by As(2)O(3) were different significantly in dose-dependent and time-dependent manners (P < 0.05). Within a certain concentration range, 3AO/cDDP apoptosis inducing rates by As(2)O(3) were dose -and time- dependent, and the most appropriate concentration was 3.0 micromol/L; lower concentrations of As(2)O(3) perturbed the cells to progress through S/G(2) phase, while higher concentrations of As(2)O(3) selectively induced apoptosis of S phase cells. As(2)O(3) up-regulated Fas gene expression, but did not affect FasL gene expression in both cell lines without significant difference (P > 0.05). Morphological observation indicated that As(2)O(3) induced typical apoptotic bodies in 3AO/cDDP and 3AO cells. CONCLUSION: As(2)O(3) effectively inhibits the proliferation of drug-resistant human ovarian carcinoma cell line through up-regulating Fas gene expression and inducing apoptosis of cells in S phase.