Campothecin suppresses cell proliferation and migration in head and neck squamous cell carcinoma by blocking RAB27A-mediated phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway.

Camptothecin (CPT), a naturally occurring alkaloid derived from the Camptotheca acuminate plant, exerts anti-tumor properties. However, its specific impact on head and neck squamous cell carcinoma (HNSCC) remains uncertain. The study was to explore the action and mechanism of CPT on HNSCC cells. First, two HNSCC cell lines (FaDu and TU686) and a normal immortalized keratinocyte (HEK001) cell line, were exposed to a spectrum of CPT concentrations (ranging from 10 to 50 µM) for durations of 24 h and 48 h. Cell viability, proliferation, migration, and invasion were assessed by CCK-8 assay, EdU incorporation assay, wound healing assay and transwell assay. Subsequently, si-RAB27A or negative control (NC) was introduced into FaDu and TU686 cells through transfection, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was manipulated with L740Y-P, an activator of this pathway. The expression of proliferating cell nuclear antigen (PCNA), E-cadherin, PI3K/AKT signaling factors and RAB27A were determined by Western blot analysis. RAB27A was detected by immunofluorescence assay. It was found that CPT significantly hindered the viability, proliferation (p<0.01), migration (p<0.001), and invasion (p<0.001) of FaDu and TU686 cells. At the molecular level, administration of CPT caused a decline in the expression of PCNA, P-PI3K, P-AKT, and RAB27A, alongside an elevation in E-cadherin levels within HNSCC cells (p<0.05, p<0.01 and p<0.001). Reducing RAB27A expression enhanced the suppressive impacts of CPT on HNSCC cell viability (p<0.05 and p<0.01), migration (p<0.001) and invasion (p<0.01), these effects that were reversed upon treatment with L740Y-P in HNSCC cells (p<0.001). In summary, our study highlights the efficacy of CPT in HNSCC, demonstrating its influence on cell processes via the RAB27A-mediated PI3K/AKT pathway.

Risk factors of common bile duct stones recurrence and nomogram for predicting recurrence after endoscopic retrograde cholangiopancreatography: a dual-center retrospective cohort study.

OBJECTIVE: Common bile duct stone (CBDS) is one of the common diseases in the digestive system, for which endoscopic retrograde cholangiopancreatography (ERCP) is a treatment procedure. However, the risk factors for CBDS recurrence after ERCP remains unclear. This study aims to compare the risk factors of CBDS recurrence after ERCP, and to set up a nomogram model to predict the long-term risk. PATIENTS AND METHODS: A retrospective analysis of 355 patients was reviewed. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. The R packages were used for the model building. The validation set contained 100 patients. RESULTS: The patients were divided into three subgroups: treated by cholecystectomy after ERCP (11.76% recurrence rate), treated without surgery after ERCP (19.70%), and with a prior history of cholecystectomy (43.64%). Each of them has different independent risk factors, and high body mass index (BMI) is correlated with an increased risk among all the subgroups. A prior history of cholecystectomy is a candidate factor that increases the risk of CBDS recurrence in patients older than 60 years, with a greater BMI, or receiving ERCP combined with EPBD. We built a nomogram model to predict the risk of long-term CBDS recurrence based on the risk factors including age, BMI, CBD diameter, the number of CBDS, and the gallbladder- or biliary tract-related events. CONCLUSIONS: CBDS recurrence is related to congenital and anatomical factors. Cholecystectomy would not be helpful to prevent CBDS recurrence, and a prior history of cholecystectomy may indicate a high risk of recurrence.

The relationship between intestinal flora changes and osteoporosis in rats with inflammatory bowel disease and the improvement effect of probiotics.

OBJECTIVE: The aim of this study was to investigate the relationship between the changes in intestinal flora and the occurrence of osteoporosis in rats with inflammatory bowel disease and the improvement effect of probiotics. MATERIALS AND METHODS: A total of 100 Sprague Dawley (SD) model rats with colitis were selected as research objects. All rats were randomly divided into two groups, including: bowel disease group and osteoporosis group, with 50 rats in each group. Stool samples were collected from all rats, and Lactobacillus, Escherichia coli and Bifidobacteria were cultured and counted. The relationship between the occurrence of related osteoporosis and intestinal flora was analyzed as well. Thereafter, the rats in osteoporosis group were randomly divided into two subgroups, namely, control group (n=25) and observation group (n=25). Observation group was treated with probiotics by gastrogavage, while the control group was treated with the same volume of physiological saline. Next, the changes in serum osteoprotegerin (OPG), osteoprotegerin ligand [receptor activator of nuclear factor-kappa B ligand (RANKL)], procollagen type I carboxy-terminal propeptide (PICP), bone mineral density (BMD), bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRACP), calcium concentration (Ca), and inflammatory cytokine levels were compared between the two groups after intervention. RESULTS: Osteoporosis group had significantly more Escherichia coli and notably fewer Lactobacillus and Bifidobacteria than bowel disease group (p<0.05). Pearson correlation analysis revealed that the occurrence of osteoporosis in rats with inflammatory bowel disease was negatively correlated with the count of Escherichia coli, whereas was positively related to the counts of Lactobacillus and Bifidobacteria (p<0.05). Moreover, the levels of serum OPG, PICP, TRACP, and Ca in observation group were remarkably higher than those in the control group (p<0.05). However, the levels of serum RANKL, BALP, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) were markedly lower than those in the control group (p<0.05). CONCLUSIONS: Osteoporosis in rats with inflammatory bowel disease has a negative association with the count of Escherichia coli, and a positive correlation with the counts of Lactobacillus and Bifidobacteria. In addition, treatment with probiotics can effectively alleviate osteoporosis symptoms in rats with inflammatory bowel disease by influencing the level of corresponding cytokines.

MiR-32-5p regulates the proliferation and metastasis of cervical cancer cells by targeting HOXB8.

OBJECTIVE: To investigate the effects of miR-32-5p on the biological behaviors of cervical cancer (CCa), the relevant mechanism was studied in CCa cell lines (HeLa) in vitro. PATIENTS AND METHODS: The expression level of miR-32-5p was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TargetScan, miRDB, microRNA databases and Luciferase method were conducted to predict and validate the target gene of miR-32-5p; the effects of miR-32-5p on cell proliferation, clone formation, invasion and migration capacity were analyzed in vitro study. RESULTS: We found miR-32-5p to be significantly inhibited in CCa tissues and cells. Bioinformatics approach together with Luciferase method screened Homeobox B8 (HOXB8) as a downstream regulatory target of miR-32-5p. Besides, HOXB8 was incredibly high expression in CCa tissues and cells. After transfection in HeLa cells by miR-32-5p mimics, HOXB8 expression was indicated to be negatively correlated with miR-32-5p both in qRT-PCR and Western blot (WB) assays. The subsequent experiments showed that decreased expression of HOXB8 resulting from up-regulation of miR-32-5p could weaken the cell proliferation, clone formation, invasion and migration ability of HeLa cells. CONCLUSIONS: MiR-32-5p could inhibit the cellular malignant behavior through regulating the expression of HOXB8 in HeLa cells. We provide a new clue for the study of molecular mechanisms of CCa. MiR-32-5p/HOXB8 axis might serve as potential target for the clinical diagnosis and treatment of CCa.

Synthesis of substituted aromatic heterocyclic sulfonyl hydrazone compounds and in vitro anti-hepatoma activity: preliminary results.

OBJECTIVE: Hydrazone compounds and their derivatives are a kind of special Schiff bases. The multiple hydrazone compounds and their derivatives have a variety of biological activities. This study aims to report the synthesis of diverse hydrazone derivatives and to explore the potent antitumor activities. MATERIALS AND METHODS: A series of aromatic heterocyclic sulfonyl hydrazones W1-W15 synthesized from hydrazine or acylhydrazine and aldehydes or ketones were estimated for their in vitro antitumor activities against human cancers. Through the spectral (FT-IR, 1H-NMR, MS) methods, the structure of the compounds was determined. Using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method, the effects of different concentrations of compounds on growth inhibition and viability of HepG-2 cells were detected. RESULTS: Compound W9 exhibited anti-proliferation activity with IC50 values of 63.91 µmol/L in HepG-2 cell line. In addition, mechanism studies indicated that compound W9 could distinctly prohibit the propagation of HepG-2 cells by arresting the cell cycle at G2/M and inducing apoptosis. Furthermore, we investigated the effectiveness of drug combination treatment with W9 and cis-platinum (cis-DDP) or 5-fluorouracil (5-FU) on HepG-2 cell line. CONCLUSIONS: Our results indicated that W9 with synergic treatment of 5-FU or cis-DDP shows better inhibitory cell growth. The combination of the two drugs blocks HepG-2 cells in the G2/M phase. The inhibitory effect of W9 on cell apoptosis was decreased with the increase of drug concentration.

LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway.

OBJECTIVE: The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that plays a key role in the malignant phenotype of tumors. Although abnormal regulation of lncRNA MALAT1 impacts clinical prognostic and tumor metastasis, its function remains unclear in ovarian cancer. PATIENTS AND METHODS: We collected 64 samples of surgical EOC tissues and 30 samples of normal ovarian tissues at the Department of Gynecology of Harbin Medical University (Harbin, China). The 30 control samples of ovarian surface epithelial tissues were obtained from patients diagnosed with uterine fibroids and scheduled hysterectomy with oophorectomy. RESULTS: The present study discovered that MALAT1 was upregulated in tumor tissues and ovarian cancer cell lines. Further, the 5-year overall survival was higher in the lower expression of the MALAT1 group. MALAT1 inhibition impeded cell proliferation, invasion and metastasis, and promoted cell apoptosis in both in vivo and in vitro. Furthermore, silencing of MALAT1 hindered the expression of epithelial-to-mesenchymal transition (EMT)-related genes and MMPS. The evidence showed that MALAT1 induce EMT via PI3K/AKT pathway. CONCLUSIONS: Our research suggests that MALAT1 transforms metastasis in EOC and may be a prospective therapeutic target.

Paracrine effect of bone marrow mesenchymal stem cells on proliferation, apoptosis, and alpha-actin-2 expression in hepatic stellate cells.

We investigated the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) on the proliferation, apoptosis, and alpha-actin-2 (ACTA2) expression of hepatic stellate cells (HSCs), and explored the possible mechanisms of hepatocyte growth factor (HGF). We established a co-culture system by culturing BMSCs on the upper layer and HSCs on the lower layer of a 6-well Transwell plate. Normal HSCs were cultured alone as a control. Cell apoptosis was determined by flow cytometry. We detected the expression of ACTA2 mRNA and ACTA2 protein in HSC using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. ACTA2 in HSCs was detected by fluorescent staining, and HGF in the co-culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The apoptotic rate of HSCs in the experiment group was 2.6 times that in the control group (P < 0.05). The expression levels of ACTA2 mRNA and ACTA2 protein were significantly inhibited in HSCs compared with the control group (P < 0.05). HGF concentration in the co-culture supernatant was 0.43 ± 0.47 mM in the experimental group, which was significantly higher than in the control group (0.16 ± 0.43 mM) (P < 0.05). The paracrine effect of BMSCs, which was caused by the suppression of ACTA2 and HGF expression, induced HSC apoptosis.

Decreased REG1α expression suppresses growth, invasion and angiogenesis of bladder cancer.

BACKGROUND: Previous study has indicated association between REG1α and bladder cancer. The aim of this study was to investigate the role of Regenerating gene I alpha (REG1α) in bladder cancer. METHODS: The role of REG1α in bladder cancer cell proliferation, migration and VEGF-induced angiogenesis was explored in vitro and in vivo. Immunohistochemistry (IHC) analysis was assessed to determine the expression of REG1α in ten paired bladder cancer and adjacent non-cancerous tissues, and in 296 bladder cancer samples. RESULTS: Down-regulation of REG1α expression significantly reduced the proliferation, migration, invasion and VEGF-induced angiogenesis in vitro and the growth of xenograft tumors in vivo. VEGF expression in bladder cancer is associated with REG1α expression and recurrence. REG1α was overexpressed in bladder cancer tissues compared with adjacent normal samples. Patients with elevated REG1α exhibited shorter recurrence times and poor survival. CONCLUSION: Downregulation of REG1α expression can reduce tumor growth, migration, invasion and angiogenesis. Our study demonstrates that REG1α can be used as a marker of recurrence and prognosis in bladder cancer. Therefore, REG1α targeting in bladder cancer patients represents a promising therapeutic strategy.

Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis.

OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

Tegafur gimeracil oter combined with oxaliplatin for advanced colorectal cancer.

OBJECTIVE: To analyze the therapeutic actions of tegafur gimeracil oteracil combined with oxaliplatin for treating patients with advanced colorectal cancer, and its effects on the K-ras gene mutation and the CK20 mRNA. PATIENTS AND METHODS: Forty-one patients with advanced colorectal cancer from our hospital, from October 2013 to October 2014, were enrolled in this study. After obtaining consent from the hospital Ethics Committee and the patients as well as their relatives, all 41 patients were divided into two groups. The control group, which consisted of 20 cases, were treated with capecitabine combined with oxaliplatin. The study group, which comprised of 21 cases, were treated with tegafur gimeracil oteracil combined with oxaliplatin. Both groups were followed-up after six months to evaluate the treatment outcomes. RESULTS: The survival rate in the observation group was higher than that in the control group. The progression-free survival time (PFS) in the observation group was longer than that in the control group. The objective response rate (ORR) and disease control rate (DCR) were higher for the observation group. The differences had statistical significance (p < 0.05). The proportion of K-ras gene mutation in the observation group was substantially superior to that in the control group. The positive expression rate of CK 20 mRNA in the observation group was significantly lower than that in the control group. The differences had statistical significance (p < 0.05). The incidence of adverse reaction in the observation group was lower than that of the control group, and the differences had statistical significance (p < 0.05). CONCLUSIONS: Tegafur/gimeracil/oteracil combined with oxaliplatin therapy had better treatment outcomes than capecitabine combined oxaliplatin for advanced colorectal cancer. This maybe related to K-ras gene mutation and the reduction of CK20 mRNA expression.

Thulium laser resection for bladder neck obstruction in women.

AIM: The aim of this paper was to investigate the efficacy of thulium laser resection of bladder neck in women with bladder neck obstruction (BNO). METHODS: Clinical information of 86 women with BNO who were treated in our hospital from Jan 2011 to Dec 2012 was retrospectively reviewed; 46 patients received thulium laser resection (group 1), and the remaining patients were treated with standard electric resection (group 2). Maximum urinary flow rate (MFR), residual urine volume (RV), overactive bladder symptom score (OABSS) and quality of life (QOL) were determined before and after surgery. These patients were followed up at 1 week, 3 months, and 12 months after surgery. RESULTS: The RV levels after surgery in groups 1 were significantly lower than those before operation. MFR significantly increased after surgery when compared with preoperation, OABSS and QOL score markedly decreased at 3 months after surgery (P<0.05). Thulium laser resection had advantages in postoperative catheter retaining time (2.18±0.73 d vs. 4.24±1.01 d), postoperative hospitalization time (3.25±0.61 d vs. 4.73±1.41 d), Intraoperative blood loss (11.5±1.53 mL vs. 32.32±8.53 mL) and total cost ($1415±71 vs. $1148±59) over standard electric resection (P<0.05), but the operative time was comparable between two groups (18.36±5.45 min vs. 19.25±7.08 min) (P >0.05). In group 2, urethral stricture was seen in 1 patient, and two patients suffered from temporary incontinence, being back to normal in one month. However, urethral stricture and incontinence were not observed in group 1. CONCLUSION: Thulium laser resection is a simple, safe and effective strategy for the treatment of bladder neck obstruction in women.

Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one binding protein (NOB1).

BACKGROUND: Nin one binding protein (NOB1) was identified as a potential oncogene in human glioma and miR-646 plays an important role in human growth and development. However, the underlying molecular mechanisms of NOB1 in tumorigenicity and its correlation with miR-646 in renal cell carcinoma (RCC) have not been investigated. METHODS: We performed bioinformatic analysis to explore miRNA targeting NOB1. The expression of NOB1 and miR-646 from 100 cases of clear cell RCC (ccRCC) and 30 cases of adjacent non-tumour tissues were detected by quantitative real-time PCR. The expression of miR-646 was correlated with NOB1 expression, tumour features and patient metastasis-free survival. The effect of overexpression of mir-646 on renal cancer cell proliferation was detected by colony formation in soft agar. Using a xenograft tumour model, we observed the in vivo tumorigenesis effect of miR-646 and NOB1. RESULTS: miR-646 negatively regulated NOB1 and inhibited the proliferation and migration of renal cancer cells. There was a significant upregulation of NOB1 in ccRCC and it was further increased in metastatic cases, while miR-646 was downregulated in tumour tissues and further decreased in metastatic ccRCC. Additionally, expression of miR-646 was inversely correlated with the expression of NOB1. The downregulation of miR-646 also indicated a higher probability of developing metastasis. Most importantly, miR-646 expression was an independent predictor of ccRCC metastasis by the univariate analysis and binary logistic regression model (both P<0.05). Colony formation in soft agar and xenograft tumour model suggested that miR-646 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, suppression of NOB1 increased the phosphorylation of several proteins in MAPK pathway. CONCLUSIONS: Downregulated miR-646 in ccRCC was associated with tumour metastasis through MAPK pathway by targeting NOB1. miR-646 and NOB1 may play an important role in the development of ccRCC.

Transcriptome profiling of prostate tumor and matched normal samples by RNA-Seq.

BACKGROUND: RNA-Sequencing (RNA-Seq) has greatly influenced cancer researches, and it provides an unprecedented resolution in estimating gene expression and has less signal noises compared to cDNA microarray. AIM: We aimed to identify a list of protein-coding genes and lincRNAs that are expressed differentially between tumor and normal tissues. MATERIALS AND METHODS: In this study, we analyzed including 10 human prostate tumor tissues and their matched normal tissues transcriptome dataset generated by recently developed RNA-Seq technology. RESULTS: By aligning short reads to human RefSeq genes and lincRNAs, we identified 10 RefSeq genes that were differentially expressed between tumor and normal samples with a p-value < 0.05, which were sufficiently enough to distinguish these two groups. Further loosing the p-value cutoff to 0.1 identified an lincRNA which is antisense to Cullin-associated and neddulation-dissociated 1 (CAND1), whose expression is repressed in prostate tumor cells. By examining the expression of CAND1 and its antisense lincRNA in the transcriptome dataset, we found an interaction between them as high expression of CAND1 and low expression of lincRNA is normal samples, and verse visa in tumor samples. CONCLUSIONS: These findings suggest the important usage of RNA-Seq in cancer studies for biomarker development and functional investigation.

Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma.

INTRODUCTION: The MHC class i chain-related molecule A (MICA) is a ligand for the natural killer group 2, member D (NKG2D) immunoreceptor activation. The engagement of tumor cell surface MICA to NKG2D stimulates the NK and T cell antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune evasion, which might partially contribute to tumor progression. MATERIAL AND METHODS: Inmunohistochemistry was performed on both normal and neoplastic renal tissue. Human renal carcinoma cell lines 786-0 and ACHIN were transfected and target sequences to silence human MMP2 by shRNA expression were established. The degree of MICA shedding was measured and quantitative real-time PCR and Western-blot analysis were performed. RESULTS: The membrane type matrix metalloproteinase 2 (MMP2) mediated the MICA shedding, which was blocked by suppression of MMP2 expression. Concomitantly, MMP2 over-expression enhanced the MICA shedding, indicating that MMP2 was involved in the renal cell carcinoma-associated proteolytic release of soluble MICA (sMICA), which facilitated the tumor immune escape. CONCLUSIONS: These findings suggested that MMP2 might be a new potential target for tumor immune therapy. Elucidation of the mechanisms by which tumors shed MICA could be of a great importance for cancer treatment in order to reinforce the NK and T cell antitumor immunity.

A computational bioinformatics analysis of gene expression identifies candidate agents for prostate cancer.

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males worldwide. Although great progress has been made, the molecular mechanisms of prostate cancer are far from being fully understood and treatment of this disease remains palliative. In this study, we sought to explore the molecular mechanism of prostate cancer and then identify biologically active small molecules capable of targeting prostate cancer using a computational bioinformatics analysis of gene expression. A total of 3068 genes, involved in cell communication, development, localisation and cell proliferation, were differentially expressed in prostate cancer samples compared with normal controls. Pathways associated with signal transduction, immune response and tumorigenesis were dysfunctional. Further, we identified a group of small molecules capable of reversing prostate cancer. These candidate agents may provide the groundwork for a combination therapy approach for prostate cancer. However, further evaluation for their potential use in the treatment of prostate cancer is still needed.

GATA-3 is down-regulated in patients with clear cell renal carcinoma.

BACKGROUND: GATA-3 is a transcription factor involved in human growth and development. Recent studies found its association with breast cancer, however, its expression profile in renal cell carcinoma (RCC) has not been investigated. MATERIAL AND METHOD: The study included 35 patients submitted to radical nephrectomy with confirmed pathological diagnosis of RCC. Normal control kidney tissues were obtained from 25 living kidney donors and tissues were biopsied before implantation. The majority of RCC samples were diagnosed as clear cell renal cell carcinoma (94.3%) except for 1 case of papillary RCC and 1 case of collecting duct carcinoma. GATA-3 expression was evaluated by quantitative PCR and Western blotting (WB) in RCC samples and normal kidneys respectively, immunohistochemical staining was performed as well. Meanwhile, the GATA-3 expression in two cancer cell lines (786-O, ACHN) and normal kidney epithelial cells (HK-2) was detected by PCR and WB. In addition, renal cancer cells and HK-2 cells were cultivated and detected by confocal microscopy for the exact intra-cellular localization of GATA-3. RESULTS: Data showed a significant down-regulation of GATA-3 expression present in neoplastic tissues compared with normal tissues; similarly, GATA-3 was significantly attenuated in all renal cancer cell lines compared with normal HK-2 cells. Confocal displayed a strong cytoplasmic immno-fluorescence activity of GATA-3 with peri-nuclear zone in HK-2, whereas the intensity in cancer cells was markedly weaker than that of HK-2. CONCLUSIONS: In summary, our present study clarifies that the aberrant expression profile of GATA-3 in human RCC is possibly involved with tumorigenesis, and the complicated mechanism is worthy of further investigation.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer.

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3ß. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.