BackgroundPatients with type 2 diabetes mellitus (T2DM) have a high incidence of renal cell carcinoma (RCC) and high sodium glucose co-transporters 2 (SGLT2) expressions. The purpose of this study was to evaluate the anticancer activity of dapagliflozin as an SGLT2 inhibitor on RCC cell lines in vitro and in vivo.Material/MethodsqRT-PCR and Western blot were used to detect SGLT2 expression on different human renal cells. Then, flow cytometry and immunofluorescence were used to investigate the effects of dapagliflozin on cell cycle, apoptosis, and SGLT2 expression of CaKi-1 cells. Finally, a xenograft model and immunohistochemical staining were used to investigate the function of dapagliflozin in nude mice.ResultsWe proved that SGLT2 is highly expressed in RCC cell lines. We found that dapagliflozin exerts a higher cytotoxic effect on human RCC than on normal human renal cells, regulates the cell cycle and apoptosis, and reduces the glucose uptake and SGLT2 expression of CaKi-1 cells. Moreover, dapagliflozin inhibits tumor growth and reduces SGLT2 expression in vivo.ConclusionsOur results indicate that dapagliflozin has high efficiency and low toxicity and could be a new therapeutic target for RCC.

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Resolvins, an endogenous lipid mediator derived from eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) of fish oil, has been reported to have anti-inflammatory and antitumor effect in various pathogenic processes. However, there are no studies about the effects of resolvin D1 and E1 on concanavalin A-induced hepatitis. Hence, the present study is to illustrate whether resolvin D1 and E1 inhibit concanavalin A-induced liver injury, liver cancer and underlying mechanisms by which they may recover. C57BL/6 mice were pretreated with resolvin D1 and E1 for 4 h, and then injected with concanavalin A for 12 h. Subsequently, blood and liver tissue were collected at 0, 2, 4, 8 and 12 h for different analysis. Analysis of inflammatory cytokines indicated that the inhibition of necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-1β and IL-6 could be performed by resolvin D1 and E1. Moreover, Toll-like receptor (TLR) 4 expression, NF-κB and AP-1 activity also have been confirmed to have key roles in the development of liver injury. They were significantly suppressed in the treatment group, compared to model. In addition, resolvin D1 and E1 markedly downregulated CD4+ and CD8+ cell infiltration in the liver. A long-term concanavalin A treatment for 32 weeks was performed to analyze the changes of hepatitis to liver cancer and the antitumor effect of resolving D1 and E1. These results indicated that resolvin D1 and E1 prevent concanavalin A-induced liver injury and the changes of hepatitis to liver cancer in mice through inhibition of inflammatory cytokine secretion and NF-κB/AP-1 activity. Thus, they could be novel target to be considered in the process of finding sufficient drug to protect against various forms of hepatitis and liver cancer.

All these results indicate that lncRNA AB073614 can induce the expression of EMT cell markers and regulate the process of EMT of CRC cells through regulating the JAK/STAT3 pathway activation.

microRNAs (miR) can potentially be used for categorizing the various subtypes of colorectal cancer (CRC) and predicting a patient's response to treatment with traditional anti-CRC therapies. We investigated how miR-1297 and its potential target molecule cyclin D2 (CCND2) might affect the progression of CRC. Thirty-two pairs of CRC specimens and corresponding samples of para-tumor tissue were collected and examined for their levels of miR-1297 and CCND2 expression. We also examined miR-1297 and CCND2 expression in cultured SW480 cells. The effects of modulated levels of miR-1297 and CCND2 on cell viability, anchorage-independent growth ability, proliferation, apoptosis, cell cycle distribution, migration, and invasion were detected using specific techniques. The possible regulatory effect of miR-1297 on CCND2 was investigated using dual luciferase assays. Our results showed that miR-1297 expression was downregulated in clinical CRC specimens, and such downregulation was associated with upregulated levels of CCND2 expression. Upregulation of miR-1297 and downregulation of CCND2 reduced the proliferation and metastasis potential of SW480 cells, but did not affect the apoptotic process. In addition, miR-1297 regulated CCND2 function by directly binding to the promoter sequence of the CCND2 gene, which would block CCND2-related signaling at the transcription level. Our findings validate the anti-CRC function of miR-1297 and pro-CRC function of CCND2. Our findings may assist in developing miR-based therapies against CRC.