Abstract Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a highly effective and well-tolerated antidiabetic drug. In addition to hypoglycemic effects, empagliflozin has many other effects, such as being hypotensive and cardioprotective. It also has anti-inflammatory and antioxidative stress effects in diabetic nephropathy. Several studies have shown that empagliflozin has anticancer effects. SGLT2 is expressed in a variety of cancer cell lines. The SGLT2 inhibitor empagliflozin has significant inhibitory effects on certain types of tumor cells, such as inhibition of proliferation, migration and induction of apoptosis. In conclusion, empagliflozin has promising applications in cancer therapy as a drug for the treatment of diabetes and heart failure. This article provides a brief review of the anticancer effects of empagliflozin.
Troxerutin, a trihydroxyethylated derivative of rutin, has been well-demonstrated to exert hepatoprotective properties. In the present study, we attempted to explore whether the antioxidant and anti-inflammatory mechanisms were involved in troxerutin-mediated protection from d-gal-induced liver injury. The effects of troxerutin on liver lipid peroxidation, antioxidant enzymatic activities, and the expression of inflammatory mediator were investigated in d-gal-treated mice. The results showed that troxerutin largely attenuated the d-gal-induced TBARS content increase and also markedly renewed the activities of Cu, Zn-SOD, CAT, and GPx in the livers of d-gal-treated mice. Furthermore, troxerutin inhibited the upregulation of the expression of NF-κB p65, iNOS, and COX-2 induced by d-gal. d-Gal-induced tissue architecture changes and serum ALT and AST increases were effectively suppressed by troxerutin. In conclusion, these results suggested that troxerutin could protect the mouse liver from d-gal-induced injury by attenuating lipid peroxidation, renewing the activities of antioxidant enzymes and suppressing inflammatory response. This study provided novel insights into the mechanisms of troxerutin in the protection of the liver.
// Zi-Feng Zhang 1, * , Yong-Jian Wang 1, * , Shao-Hua Fan 1 , Shi-Xin Du 2 , Xue-Dong Li 2 , Dong-Mei Wu 1 , Jun Lu 1 and Yuan-Lin Zheng 1 1 Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, P.R. China 2 Department of Orthopedics, The Third Affiliated Hospital, Shenzhen University, Shenzhen 518002, P.R. China * Co-first authors Correspondence to: Dong-Mei Wu, email: wdm8610@jsnu.edu.cn Jun Lu, email: lu-jun75@163.com Yuan-Lin Zheng, email: ylzheng@jsnu.edu.cn Keywords: microRNA-182, homeobox A9, wingless-type/β-catenin signaling pathway, osteosarcoma Received: April 14, 2017 Accepted: September 04, 2017 Published: September 22, 2017 ABSTRACT We investigated the mechanisms by which microRNA (miR)-182 promotes apoptosis and inhibits proliferation in human osteosarcoma (OS) cells. Levels of miR-182 and Homeobox A9 (HOXA9) expression were compared between human OS and normal cells. Subjects were divided into OS and normal groups. We analyzed the target relationship of miR-182 and Homeobox A9 (HOXA9). Cells were then assigned into blank, negative control, miR-182 mimics, miR-182 inhibitors, siRNA-HOXA9, or and miR-182 inhibitors + siRNA-HOXA9 groups. Cell function was assayed by CCK-8, flow cytometry and wound healing assay. Additionally, we analyzed OS tumor growth in a xenograft mouse model. Dual-luciferase reporter assays indicated miR-182 directly targets HOXA9. Reverse transcription quantitative PCR and western blotting revealed elevated expression of miR-182, WIF-1, BIM, and Bax, and reduced expression of HOXA9, Wnt, β-catenin, Survivin, Cyclin D1, c-Myc, Mcl-1, Bcl-xL, and Snail in osteosarcoma cells treated with miR-182 mimic or siRNA-HOXA9 as compared to controls. Osteosarcoma cells also exhibited decreased cell proliferation, migration, and tumor growth, and increased apoptosis when treated with miR-182 mimic or siRNA-HOXA9. Correspondingly, in a xenograft mouse model, osteosarcoma tumor volume and growth were increased when cells were treated with miR-182 inhibitor and decreased by miR-182 mimic or siRNA-HOXA9. These results indicate that miR-182 downregulates Wnt/β-catenin signaling, inhibits cell proliferation, and promotes apoptosis in osteosarcoma cells by suppressing HOXA9 expression.
// Yong-Jian Wang 1, * , Zi-Feng Zhang 1, * , Shao-Hua Fan 1 , Juan Zhuang 1, 2, 3 , Qun Shan 1 , Xin-Rui Han 1 , Xin Wen 1 , Meng-Qiu Li 1 , Bin Hu 1 , Chun-Hui Sun 1 , Bin Qiao 4 , Qian Tao 4 , Dong-Mei Wu 1 , Jun Lu 1 and Yuan-Lin Zheng 1 1 Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, P.R. China 2 School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, P.R. China 3 Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, School of Life Sciences, Huaiyin Normal University, Huaian 223300, P.R. China 4 Department of Oral and Maxillofacial Surgery, Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Oral Diseases, Sun Yat-Sen University, Guangzhou 510055, P.R. China * These authors have contributed equally to this work Correspondence to: Dong-Mei Wu, email: wdm8610@jsnu.edu.cn Jun Lu, email: lu-jun75@163.com Yuan-Lin Zheng, email: ylzheng@jsnu.edu.cn Keywords: oral squamous cell carcinoma; SCC-9 cell; microRNA-433; FAK; ERK Received: March 01, 2017 Accepted: October 05, 2017 Published: October 27, 2017 ABSTRACT We investigated the involvement of microRNA-433 (miR-433) in the proliferation, migration, and invasiveness of oral squamous cell carcinoma (OSCC). Totally 108 OSCC tissues and adjacent normal tissues from patients with OSCC were collected. Also, transplanted tumor formation experiment in nude mice was conducted to verify the effect of miR-433 and FAK on subcutaneous transplanted tumor. The CD44 + stem cell from SCC-9 were collected and assigned into the blank, miR-433 mimics, mimics control, miR-433 inhibitors, inhibitors control, siFAK and miR-433 inhibitors + siFAK groups. The qRT-PCR and western blotting were used to detect miR-433, FAK, ERK, MEK, pERK and pMEK after transfection. Flow cytometry, MTT assay, scratch test and Transwell assay were performed to determine the cell proportion, growth, migration and invasion of SCC-9 cells. In cell line SCC-9, expression of CD133, Oct-4, and BIM-1 was greater in CD44 + cells than CD44 - cells, indicating that CD44 + cells had characteristics of tumor stem cells. Expression of FAK, ERK, MEK, p-ERK and p-MEK was decreased in tumor tissues from the CD44 - , miR-433, and siFAK groups. Expression of MiR-433 mRNA was elevated, while levels of FAK, ERK, MEK, p-ERK, and p-MEK mRNA were all decreased in the miR-433 mimics group. In the miR-433 mimics and siFAK groups, cell proliferation, migration, and invasion were all decreased, while the opposite trends were seen in the miR-433 inhibitor group. These results indicate that miR-433 downregulates FAK through the ERK/MAPK signaling pathway to inhibit the proliferation, migration, and invasiveness of SCC-9 OSCC cells.
This study investigates the protective effects of miR-431 against cerebral ischemia-reperfusion injury through the Rho/Rho-kinase signaling pathway. SD rats were randomly classified into normal, sham, and model (middle cerebral artery occluded) groups. Rho expression and cerebral infarction were visualized by immunohischemistry and TTC staining, respectively. qRT-PCR and western blotting were used to measure mRNA and protein expression of miR-431 and Rho/Rho-kinase signaling pathway-related genes. Hippocampal neurons were extracted and assigned into normal, blank, negative control (NC), miR-431 mimics, miR-431 inhibitors, siRNA-Rho, and miR-431 inhibitors + siRNA-Rho groups. Proliferation and apoptosis were detected by MTT and flow cytometry, respectively. Compared with the normal group, the model group showed elevated Rho expression, area of cerebral infarction, and expressions of Rho/Rho-kinase related genes but reduced miR-431 expression. Compared with the blank group, expression of Rho, Rho-kinase α, and Rho-kinase β decreased and miR-431 expression increased in the miR-431 mimics and siRNA-Rho groups, and the tendency reversed in the miR-431 inhibitors group. Enhanced proliferation and inhibited apoptosis were exhibited in the miR-431 mimics and siRNA-Rho groups while results in the miR-431 inhibitors group reversed. Findings obtained from this study indicated that miR-431 confers protection against cerebral ischemia-reperfusion injury through negatively regulating the Rho/Rho-kinase signaling pathway.
Abstract Ectodermal‐neural cortex 1 (ENC1) belongs to a member of the kelch family of genes. It is an actin‐binding protein and plays a pivotal role in neuronal and adipocyte differentiation. Here, we found that lower expression of ENC1 in the ovarian cancer patients was associated with favorable prognosis. In addition, ENC1 was heterogeneously expressed in various ovarian cancer cells. The messenger RNA and protein expression levels of ENC1 in HO‐8910PM and NIH:OVCAR‐3 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of ENC1 in HO‐8910PM or NIH:OVCAR‐3 cells could significantly increase the reactive oxygen species levels, resulting in inhibition of in vitro proliferation, migration, and invasion. Our findings suggest that decreasing expression of ENC1 may be a new approach that can be used for ovarian cancer treatment.
We explored the effect of S100A12 gene on serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by activating the extracellular signal-regulated kinase (ERK) signaling pathway. A total of 180 specific pathogen-free (SPF) rats were purchased to establish cecal ligation and puncture (CLP) model. Rats were assigned into the sham, model, empty vector, S100A12 siRNA, epidermal growth factor (EGF), and S100A12 siRNA + EGF groups. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB in liver tissues of rats among six groups were detected by RT-qPCR and western blotting. ELISA was used to determine serum levels of IL-1β, IL-10, TNF-α, procalcitonin (PCT), and C-reactive protein (CRP). Pearson correlation analysis was conducted to measure correlations. Cell apoptosis of rats among six groups was detected by Tunel staining. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB decreased in the S100A12 siRNA group while increased in the EGF group compared with the model group. S100A12 mRNA expression was positively correlated with mRNA expressions of related genes in the ERK signaling pathway (ERK-1, ERK-2, cPLA2, and NF-κB) in the model and empty vector groups. Expressions of IL-1β, IL-6, TNF-α, PCT, and CRP in the EGF group were higher than those in the model group, but were lower than those in the S100A12 siRNA group. Compared with the model group, cell apoptosis decreased in the S100A12 siRNA group but that increased in the EGF group. We demonstrates that S100A12 gene silencing decreases serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by inhibiting the ERK signaling pathway.
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