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Metformin-conjugated micellar system with intratumoral pH responsive de-shielding for co-delivery of doxorubicin and nucleic acid.
Abstract A novel PMet-P(cdmPEG2K) polymeric micellar carrier was developed for tumor-targeted co-delivery of DOX and nucleic acids (NA), based on polymetformin and a structure designed to lose the PEG shell in response to the acidic extracellular tumor environment. NA/DOX co-loaded micelleplexes exhibited enhanced inhibition of cell proliferation compared to DOX-loaded micelles, and displayed a higher level of cytotoxicity at an acidic pH (6.8) which mimicks the tumor microenvironment. The PMet-P(cdmPEG2K) micelles achieved significantly improved transfection with either a reporter plasmid or Cy3-siRNA, and enhanc...
Source: Biochemical Pharmacology - February 2, 2021 Category: Drugs & Pharmacology Authors: Liu Y, Sun J, Huang Y, Chen Y, Li J, Liang L, Xu J, Wan Z, Zhang B, Li Z, Li S Tags: Biochem Pharmacol Source Type: research

Metformin Relieves Bortezomib-Induced Neuropathic Pain by Regulating AMPKa2-Mediated Autophagy in the Spinal Dorsal Horn
Neurochem Res. 2022 Mar 12. doi: 10.1007/s11064-022-03571-7. Online ahead of print.ABSTRACTChemotherapy-induced neuropathic pain is a major clinical problem with limited treatment options. Here, we show that metformin relieves bortezomib (BTZ)-evoked induction and maintenance of neuropathic pain by preventing the reduction in the expression of Beclin-1, an autophagy marker, in the spinal dorsal horn. Application of rapamycin or 3-methyladenine, autophagy inducer and inhibitor, respectively, affected the mechanical allodynia differently. Co-application of 3-methyladenine and metformin partially inhibited the effect of metfo...
Source: Neurochemical Research - March 12, 2022 Category: Neuroscience Authors: Meng Liu Yu-Ting Zhao You-You Lv Ting Xu Dai Li Yuan-Chang Xiong Wen-Jun Xin Su-Yan Lin Source Type: research

Abstract 16: Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necroptosis in C4-2B osseous metastatic castration-resistant prostate cancer cells
Castration-resistant prostate cancer (CRPC) cells acquire resistance to chemotherapy and apoptosis in part due to enhanced aerobic glycolysis and biomass production, known as Warburg effect. We previously demonstrated that combination simvastatin (SIM) and metformin (MET) ameliorates critical Warburg effect-related metabolic aberrations of C4-2B cells, synergistically and significantly decreases CRPC cell viability and metastatic properties, with minimal effect on normal prostate epithelial cells, and inhibits primary prostate tumor growth, metastasis, and biochemical failure in an orthotopic model of metastatic CRPC, more...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Babcook, M. A., Sramkoski, R. M., Fujioka, H., Daneshgari, F., Almasan, A., Shukla, S., Gupta, S. Tags: Molecular and Cellular Biology Source Type: research

Down ‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer
This study aims to investigate the effect of down‐regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p‐AMPK and p‐STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan‐Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in b...
Source: Journal of Cellular and Molecular Medicine - March 1, 2018 Category: Molecular Biology Authors: Qiongli Su, Ting Tao, Lei Tang, Jun Deng, Kwame Oteng Darko, Sichun Zhou, Mei Peng, Shanping He, Qing Zeng, Alex F. Chen, Xiaoping Yang Tags: ORIGINAL ARTICLE Source Type: research

Down-regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer.
This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p-AMPK and p-STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan-Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder c...
Source: J Cell Mol Med - March 7, 2018 Category: Molecular Biology Authors: Su Q, Tao T, Tang L, Deng J, Darko KO, Zhou S, Peng M, He S, Zeng Q, Chen AF, Yang X Tags: J Cell Mol Med Source Type: research

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1 α in NSCLC which can be overcome by OXPHOS inhibition.
CONCLUSION: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors. PMID: 30880247 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - March 13, 2019 Category: Biology Authors: Cruz-Bermúdez A, Laza-Briviesca R, Vicente-Blanco RJ, García-Grande A, Coronado MJ, Laine-Menéndez S, Palacios-Zambrano S, Moreno-Villa MR, Ruiz-Valdepeñas AM, Lendinez C, Romero A, Franco F, Calvo V, Alfaro C, Acosta PM, Salas C, Garcia JM, Provencio Tags: Free Radic Biol Med Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

CXCR3 confers sorafenib resistance of HCC cells through regulating metabolic alteration and AMPK pathway.
Authors: Ren Y, Gu YK, Li Z, Xu GZ, Zhang YM, Dong MX, Wang Y, Zhou XB Abstract Currently, the acquired resistance of the hepatocellular carcinoma (HCC) first-line therapeutic agent-sorafenib (SOR) remains a major challenge for HCC management. Recent evidence suggested the association between CXCL/CXCRs chemokines and chemotherapy resistant in cancer cells. Hence, exploring the internal mechanism of CXCRs involved in SOR resistance will help to improve the efficacy of HCC. SOR-resistant HCC cells (Huh7-SOR) were established through escalating concentration of SOR. Glucose consumption, lactate production, intracellu...
Source: American Journal of Translational Research - April 11, 2020 Category: Research Tags: Am J Transl Res Source Type: research