Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

https://www.mdpi.com/1422-0067/21/11/4002/pdf

Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.

Inhibitory effects of Paris saponin I, II, VI and VII on HUVEC cells through regulation of VEGFR2, PI3K/AKT/mTOR, Src/eNOS, PLCγ/ERK/MERK, and JAK2-STAT3 pathways.

Immunotherapy has emerged as one of the most promising treatments for cancer in recent years. However, it works only for a small proportion of patients, which can in part be attributed to the immunosuppressive tumor microenvironment (TME). Tumor associated macrophages (TAMs) are the critical components of tumors and play an important role in the development of the immunosuppressive TME. The transition of TAMs from the pro-tumor (M2) phenotype to anti-tumor (M1) phenotype is crucial for the immunotherapy of gastric cancer. Herein, we developed a shear-thinning, injectable hydrogel co-loaded with polyphyllin II (PP2) and resiquimod (R848) (PR-Gel) for potentiating localized immunotherapy of gastric cancer through the repolarization of TAMs. In this work, we evaluate the effects of PR-Gel on TAM repolarization and explored its therapeutic effect for localized immunotherapy. The hydrogels were synthesized through the Schiff base reactions between aldehyde-functionalized polyethylene glycol and the amino group of polylysine. A M2-to-M1 repolarization of TAMs and increased production of TNF-α and IL-6 were observed after treatment with PR-Gel in vitro. The anti-tumor efficacy of PR-Gel in a subcutaneous xenograft model of gastric cancer showed that the hydrogels possess good tumor growth suppression properties after a single injection. Furthermore, an increased iNOS/CD206 ratio in TAMs and enhanced CD8+ T cell infiltration were also observed within the TME after the treatment with PR-Gel. Hence, the biocompatible, shear-thinning, injectable hydrogels are a promising noninvasive drug-delivery platform for the regulation of the immunosuppressive TME and have great potential in localized immunotherapy against gastric cancer.

Injectable shear-thinning polylysine hydrogels for localized immunotherapy of gastric cancer through repolarization of tumor-associated macrophages.

Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells

Autophagy is an evolutionarily conserved self-degradation system that recycles cellular components and damaged organelles, which is critical for the maintenance of cellular homeostasis. Intracellular reactive oxygen species (ROS) are short-lived molecules containing unpaired electrons that are formed by the partial reduction of molecular oxygen. It is widely known that autophagy and ROS can regulate each other to influence the progression of cancer. Recently, due to the wide potent anti-cancer effects with minimal side effects, phytochemicals, especially those that can modulate ROS and autophagy, have attracted great interest of researchers. In this review, we afford an overview of the complex regulatory relationship between autophagy and ROS in cancer, with an emphasis on phytochemicals that regulate ROS and autophagy for cancer therapy. We also discuss the effects of ROS/autophagy inhibitors on the anti-cancer effects of phytochemicals, and the challenges associated with harnessing the regulation potential on ROS and autophagy of phytochemicals for cancer therapy.

/pdf/targeting-the-interplay-of-autophagy-and-ros-for-cancer-3f345zpi.pdf

Zhuo-Qun Wang

Papers

Anti-cancer effects of Polyphyllin I: An update in 5 years

Medicinal plants and their secondary metabolites in alleviating knee osteoarthritis: A systematic review.

Asparaginase-associated pancreatitis in chemotherapy-treated pediatric patients: a five-year retrospective study.