The Nrf2/Keap1 pathway is an important signaling cascade responsible for the resistance of oxidative damage induced by exogenous chemicals. It maintains the redox homeostasis, exerts anti‐inflammation and anticancer activity by regulating its multiple downstream cytoprotective genes, thereby plays a vital role in cell survival. Interestingly, in recent years, accumulating evidence suggests that Nrf2 has a contradictory role in cancers. Aberrant activation of Nrf2 is associated with poor prognosis. The constitutive activation of Nrf2 in various cancers induces pro‐survival genes and promotes cancer cell proliferation by metabolic reprogramming, repression of cancer cell apoptosis, and enhancement of self‐renewal capacity of cancer stem cells. More importantly, Nrf2 is proved to contribute to the chemoresistance and radioresistance of cancer cells as well as inflammation‐induced carcinogenesis. A number of Nrf2 inhibitors discovered for cancer treatment were reviewed in this report. These provide a new strategy that targeting Nrf2 could be a promising therapeutic approach against cancer. This review aims to summarize the dual effects of Nrf2 in cancer, revealing its function both in cancer prevention and inhibition, to further discover novel anticancer treatment.

Activated pancreatic stellate cells (PSCs) are the main effector cells in the process of fibrosis, a major pathological feature in pancreatic diseases that including chronic pancreatitis and pancreatic cancer. During tumorigenesis, quiescent PSCs change into an active myofibroblast-like phenotype which could create a favorable tumor microenvironment and facilitate cancer progression by increasing proliferation, invasiveness and inducing treatment resistance of pancreatic cancer cells. Many cellular signals are revealed contributing to the activation of PSCs, such as transforming growth factor-β, platelet derived growth factor, mitogen-activated protein kinase (MAPK), Smads, nuclear factor-κB (NF-κB) pathways and so on. Therefore, investigating the role of these factors and signaling pathways in PSCs activation will promote the development of PSCs-specific therapeutic strategies that may provide novel options for pancreatic cancer therapy. In this review, we systematically summarize the current knowledge about PSCs activation-associated stimulating factors and signaling pathways and hope to provide new strategies for the treatment of pancreatic diseases.

Background and Purpose: Renal fibrosis acts as the common pathway leading to the development of end‐stage renal disease. Previous studies have shown that resveratrol has anti‐fibrotic activity, but its potential molecular mechanisms of action are not well understood.Experimental Approach: The anti‐fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF‐β1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining.Key Results: Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast–myofibroblast differentiation (FMD) and epithelial–mesenchymal transition (EMT). The anti‐fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation‐related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/β‐catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF‐β1‐induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation‐related signalling. Similarly, TGF‐β1‐mediated overactivation of the proliferation‐related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti‐fibrotic and anti‐proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype.Conclusions and Implications: Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation‐related pathways, making it a potential therapeutic agent for preventing renal fibrosis.