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Numerous studies have suggested that microRNAs (miRNAs) are vital in the development of various types of human cancers, including renal cell carcinoma (RCC), and the regulation of tumor progression and invasion. However, the effect of miRNA-27a (miR-27a) on the tumorigenesis of RCC is unclear. The aim of the present study was to investigate the function of miR-27a and identify its possible target genes in RCC cells. In the present study, cell proliferation, migration and invasion and the percentage of apoptotic cells were detected by methylthiazol tetrazolium assays, Annexin V analysis, wound-healing assays and Transwell invasion assays. Western blot analysis was performed to validate the protein expression level and assess whether the epidermal growth factor receptor (EGFR) was a target gene of miR-27a. A tumor xenograft animal model was used to detect the role of miR-27a on RCC cell growth in vivo. The present study demonstrated that miR-27a significantly suppressed human RCC 786-O cell proliferation and induced cell apoptosis. Restoration of miR-27 also resulted in 786-O cell migration and invasion inhibition. Furthermore, upregulated miR-27a attenuated RCC tumor growth in the tumor xenograft animal model. The present results suggested that miR-27a functions as a tumor suppressor in RCC. The western blot analysis assay revealed that EGFR was a novel target of miR-27a. The growth suppression of RCC cells was attributed partly to the downregulation of the cell cycle by ERFR inhibition. The present findings may aid in the understanding of the molecular mechanism of miR-27a in the tumorigenesis of RCC, and may provide novel diagnostic and therapeutic options for RCC. [ABSTRACT FROM AUTHOR]

The concentrations required for curcumin to exert its anticancer activity (IC50, 20 μM) are difficult to achieve in the blood plasma of patients, due to the low bioavailability of the compound. Therefore, much effort has been devoted to the development of curcumin analogues that exhibit stronger anticancer activity and a lower IC50 than curcumin. The present study investigated twelve pyridine analogues of curcumin, labeled as groups AN, BN, EN and FN, to determine their effects in CWR-22Rv1 human prostate cancer cells. The inhibitory effects of these compounds on testosterone (TT)-induced androgen receptor (AR) activity was determined by performing an AR-linked luciferase assay and by TT-induced expression of prostate-specific antigen. The results of the current study suggested that the FN group of analogues had the strongest inhibitory effect of growth on CWR-22Rv1 cultured cells, and were the most potent inhibitor of AR activity compared with curcumin, and the AN, BN and EN analogues. Thus, the results of the present study indicate the inhibition of the AR pathways as a potential mechanism for the anticancer effect of curcumin analogues in human prostate cancer cells. Furthermore, curcumin analogues with pyridine as a distal ring and tetrahydrothiopyran-4-one as a linker may be good candidates for the development of novel drugs for the treatment of prostate cancer, by targeting the AR signaling pathway. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most prevalent type of primary malignant bone tumor. Inhibitor of growth 4 (ING4) has been demonstrated to function as a tumor suppressor through multiple pathways, and is its expression is understood to be suppressed or reduced in various malignancies. The present study aimed to investigate the expression of ING4 and to determine its prognostic value in osteosarcoma tissue. Formalin-fixed, paraffin-embedded tissue microarrays were analyzed, and contained 41 osteosarcoma specimens and 11 normal bone tissue specimens with duplicate cores. ING4 expression was evaluated by immunohistochemical staining. The association between ING4 expression in the osteosarcoma and normal bone tissues was analyzed, in addition to the association between ING4 expression and Enneking classification of the osteosarcoma tissues. A significant statistical difference was observed in the ING4 immunohistochemical staining score between the osteosarcoma and normal bone tissues (P<0.001). Furthermore, a significant negative correlation was detected between the ING4 immunohistochemical staining scores and the Enneking classification results of the 41 osteosarcoma tissues (P=0.002). Low expression of ING4 was observed in the osteosarcoma specimens, and this reduced expression of ING4 was negatively correlated with Enneking classification. Thus, the results of the present study indicate that ING4 may serve as a promising prognostic marker in osteosarcoma. [ABSTRACT FROM AUTHOR]

Genetic mutation of breast cancer 1 (BRCA1) is one of the most notable factors responsible for a proportion of breast cancer cases. BRCA1 encodes a 1,863-amino acid protein and functions as a negative regulator of tumor growth. Thus, investigation of the underlying mechanisms that regulate BRCA1 gene expression provide further insight into possible targets for breast cancer therapy. Previous studies have demonstrated that the genetic variants in the BRCA1 3' untranslated region (3'UTR), in addition to the cytosine-phosphate-guanine (CpG) islands in the promoter region, are significantly associated with breast cancer risk; however, the role of single nucleotide polymorphisms (SNPs) in the BRCA1 3'UTR remains unclear. The present study aimed to investigate the association between SNPs and BRCA1 mRNA expression levels. Bioinformatics analysis demonstrated that 2 SNPs in the BRCA1 3'UTR (rs12516 and rs8176318 with putative microRNA binding sites) were significantly correlated with mRNA expression in lymphoblastoid cell lines (P=2.55x10-4 and P=8.78x10-5, respectively). Furthermore, the genotype frequency distribution varied between populations worldwide. In addition, 3 CpG islands and several transcription factor binding sites in the BRCA1 promoter region were established. The identification of such polymorphisms and CpG islands may aid in designing improved therapeutic strategies to treat patients with BRCA1-associated breast cancer. [ABSTRACT FROM AUTHOR]

It has been demonstrated that microRNA-497 (miR-497) acts as a tumor suppressor and is involved in tumor progression, development and metastasis in several types of cancer. However, little is known about the exact role of miR-497 in osteosarcoma (OS). The aim of the current study was to investigate the potential role of miR-497 in human OS. The role of miR-497 in the growth and survival of OS cells was determined using several in vitro approaches and a nude mouse model. The results demonstrated that exogenous expression of miR-497 in human OS MG63 cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell arrest at the G0/G1 phase of the cell cycle. In addition, the results of the in vivo study indicated that restoration of miR-497 inhibited OS tumor growth in a nude mouse model. Overall, the results of the present study identified a crucial tumor suppressive role of miR-497 in the progression of OS, and suggested that miR-497 may be a potential therapeutic agent for the treatment of OS. [ABSTRACT FROM AUTHOR]

Neuropsychological factors have been shown to influence tumor progression and therapeutic response. The present study investigated the effect of the dopamine receptor antagonist thioridazine on murine breast cancer. The anti-tumor efficacy of thioridazine was assessed using a murine breast cancer model. Cell apoptosis and proliferation were analyzed in vitro using f low cytometry (FCM) and the MTT assay, respectively. Western blot analysis was performed to assess Akt, phosphorylated (p)-Akt, signal transducer and activator of transcription (STAT) 3, p-STAT3 and p-p65 in tumor cells following treatment with thioridazine. The Ki67 index and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells were assessed in the tumor sections. Thioridazine was found to reduce tumor growth, inhibit tumor cell proliferation and induce apoptosis in a dose- and time-dependent manner in vitro. Thioridazine was also found to markedly inhibit tumor proliferation and induce tumor cell apoptosis in vivo as shown by the lower Ki67 index and increase in TUNEL-positive cells. In addition, thioridazine was observed to inhibit the activation of the canonical nuclear factor κ-light-chain-enhancer of activated B cells pathway and exert anti-tumor effects by remodeling the tumor stroma, as well as inhibit angiogenesis in the tumor microenvironment. In conclusion, thioridazine was found to significantly inhibit breast tumor growth and the potential for thioridazine to be used in cancer therapy may be re-evaluated and investigated in clinical settings. [ABSTRACT FROM AUTHOR]

Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal squamous cell carcinoma (ESCC) and are crucial in tumorigenesis, among which miR-338-3p has been examined to be downregulated in patients with ESCC. However, the role of miR-338-3p in ESCC remains to be elucidated. In the present study, the role of miR-338-3p on the growth and survival of an ESCC cell line was determined with several in vitro approaches and in nude mouse models. It was determined that miR-338-3p expression was frequently downregulated in ESCC tissue compared with corresponding adjacent non-tumor tissue, and that its expression was significantly correlated with tumor stage and metastasis. Overexpression of miR-338-3p in ESCC cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell arrest at the G0/G1 stage and cell apoptosis in vitro. In addition, it was demonstrated that overexpression of miR-338-3p significantly suppresses tumor growth of xenograft tumors in mice (P<0.05). These findings revealed that miR-338-3p may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC. In addition, it was suggested that miR-338-3p may be a potential therapeutic agent for treatment of ESCC. [ABSTRACT FROM AUTHOR]

MicroRNA-210 (miR-210), the master hypoxamir, has various roles in the development of certain cancer types. It has been reported that miR-210 expression was upregulated in patients with osteosarcoma (OS). However, little is known regarding its role in the development of human OS. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, miR-210 inhibitor was transfected into the osteosarcoma cell line MG-63 cells, and cell proliferation, colony formation, cycle, apoptosis, migration and invasion were assessed. It was found that miR-210 downregulation significantly suppressed clonogenicity, migration and invasion, as well as induced cell apoptosis, increased the percentage of cells in G1 phrase and decreased the percentage of cells in S phase in vitro. In addition, the effect of miR-210 on tumor growth was evaluated in vivo. The results indicated that miR-210 downregulation significantly suppressed tumor growth in nude mouse models. In conclusion, the findings of the present study suggested that miR-210 is a potential therapeutic agent for the treatment of OS. [ABSTRACT FROM AUTHOR]

Malignant gliomas are the most common type of primary malignancy of the central nervous system, with a poor prognosis. The therapeutic options for malignant gliomas are limited and far from satisfactory, and novel treatment strategies are urgently required to improve the outcome of the disease. Insulin-like growth factor (IGF)/IGF-1 receptor (IGF-1R) signaling pathway regulates cell proliferation, motility and survival. The dysregulation of this signaling pathway has been implicated in the development of malignant gliomas. In the present study, GSK1904529A, a small molecule inhibitor of IGF-1R, suppressed glioma cell viability, induced glioma cell apoptosis and inhibited glioma cell migration in vitro. In addition, GSK1904529A inhibited glioma tumor growth and induced tumor cell apoptosis in vivo. In conclusion, the results of the present study suggested GSK1904529A as a promising agent for the treatment of malignant glioma. [ABSTRACT FROM AUTHOR]

Oxaliplatin (OX) has been widely used in adjuvant and palliative treatments of advanced colon cancer; however, cancer cells ultimately become resistant in the majority of cases. Therefore, the development of a novel strategy to overcome this resistance is important for the effective treatment of colon cancer. Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer; therefore, the present study used murine CT26 colon carcinoma cells to explore whether inhibition of autophagy by 3-methyladenine (3-MA) is able to enhance OX-induced apoptosis in vitro and OX-suppressed tumor growth in vivo. CT26 cells were treated with 3-MA, OX, or 3-MA plus OX, and the autophagy, apoptosis and proliferation of the CT26 cells was investigated. Additionally, the therapeutic efficiency of the combination of 3-MA and OX treatment was evaluated in vivo by determining the survival time of the tumor-bearing mice and, thus, tumor growth rate. The treatment of CT26 cells in vitro with OX alone increased autophagy as well as apoptosis, whereas treatment with 3-MA plus OX markedly inhibited OX-induced autophagy, but increased OX-induced cell apoptosis. Furthermore, the combination of OX and 3-MA treatment significantly suppressed tumor growth in vivo and prolonged mouse survival time when compared with OX treatment alone. Similarly, 3-MA increased OX-induced cell apoptosis and decreased autophagy in xenograft tumor tissues. Thus, the administration of 3-MA may increase tumor cell sensitivity to OX by reducing its autophagic effects and enhancing its apoptotic effects. Data obtained in the present study indicates that the clinical combination of an autophagy inhibitor with OX may increase the therapeutic effect of OX and improve the clinical outcome of patients with colon cancer. [ABSTRACT FROM AUTHOR]

Somatostatin (SST) is a gut peptide that is able to inhibit the growth of tumor cells in gastric cancer and other types of cancer. The present study investigated the mRNA and protein levels of SST and SST receptors (SSTRs) in human gastric cancer, and detected the DNA methylation of the SST promoter. The protein levels of SST were detected using a radioimmunoassay in 102 human gastric tissue specimens (51 pairs of samples from 51 gastric cancer patients, each pair of samples included a cancer tissue and a normal tissue sample). SST and SSTR mRNA expression was assessed by reverse transcription-PCR (RT-PCR), while SST promoter methylation was examined using quantitative methylation-specific PCR (qMSP) in 51 pairs of tissues. The association between SST protein and RNA levels and SST methylation and gastric cancer were also analyzed. The protein levels of SST were decreased in the gastric cancer group compared with those of the normal group (5.091±0.994 vs. 7.399±0.956 pg/mg; P<0.01). The RT-PCR analysis indicated that the mRNA levels of SST (0.218±0.183 vs. 0.456±0.331; P<0.001) and SSTRs in the gastric cancer group were lower compared with those of the normal gastric tissue group. The methylation proportion of SST was 45.1% (23/51) in the carcinoma group and 3.9% (2/51) in the normal group. In conclusion, SST promoter methylation is a common event in human gastric cancer and is connected with a decrease in SST protein and RNA levels and associated with gastric carcinogens. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACIs) are a promising class of drugs that act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is an HDACI that has been widely used as an anti-convulsant and shows promise as a chemotherapeutic drug for a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of bladder cancer cells and its synergistic effect with chemotherapeutic agents in vitro and in vivo. The cell viability of human bladder cancer cell lines following treatment with VPA and/or VPA in combination with mitomycin C, cisplatin (DDP) and adriamycin were determined using a 3 -(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay. Hoechst staining was used to observe the morphology of the apoptotic cells. Survivin protein and acetylated histone H3 levels were quantified using western blot analysis. The in vivo tumor growth inhibition of VPA was determined in rats with N-methyl-N-nitrosourea-induced bladder cancer. VPA significantly inhibited the growth of the bladder cancer cells in a concentration- and time-dependent manner. Furthermore, improved results were achieved for tumor inhibition when VPA was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in the bladder cancer cells following the treatment with VPA. Intravesical injections of VPA were able to inhibit tumor progression when combined with DDP. In conclusion, VPA acts as an HDACI that has a direct anticancer effect and markedly enhances the action of several chemotherapy agents. VPA may sensitize bladder cancer to anticancer drugs by downregulating survivin expression. [ABSTRACT FROM AUTHOR]