Lx2-32c, a Novel Taxane Derivative, Exerts Anti-resistance Activity by Initiating Intrinsic Apoptosis Pathway in Vitro and Inhibits the Growth of Resistant Tumor in Vivo
スポンサーリンク
概要
- 論文の詳細を見る
Resistance to anticancer drugs is a major obstacle to successful chemotherapy. Thus, the exploration of new drugs and strategies in combating resistance is of great importance. In this study, we investigated the anti-tumor drug resistance (anti-resistance for short) activity of Lx2-32c, a novel taxane, and its possible mechanisms. Lx2-32c was cytotoxic to various drug-resistant tumor cell lines, and significantly suppressed the growth of tumor xenografts in paclitaxel-resistant MX-1 nude mice. It promoted microtubule polymerization and G2/M phase arrest in MX-1/T cells. Moreover, it induced typical apoptotic characteristics indicated by morphological changes and DNA fragmentation. Apoptosis was associated with loss of mitochondrial membrane potential, enhancement of mitochondrial cytochrome c and apoptosis-inducing factor (AIF) release, elevation of the Bax/Bcl-2 ratio, activation of caspase-9,-3 but not caspase-8 and Fas/FasL, and degradation of poly(ADP-ribose) polymerase (PARP). In conclusion, Lx2-32c is an effective microtubule-stabilizing agent in overcoming paclitaxel resistance by inducing apoptosis via the intrinsic apoptotic pathway. It also displayed robust anti-paclitaxel-resistance activity in vivo. Therefore, these findings provide new insight into the strategy to overcome resistance by manipulating dysregulated apoptosis pathway.
著者
-
Zhou Qing
Department Of Anesthesia Critical Care Medicine & Emergency Medicine Center Zhongnan Hospital Wu
-
Chen Xiaoguang
Department Of Pharmacology Institute Of Materia Medica Chinese Academy Of Medical Sciences And Pekin
-
Jin Jing
Department Of Chemistry And Chemical Biology Baker Laboratory Cornell University
-
Li Yan
Department Of Applied Chemistry Graduate School Of Engineering Kyushu University
-
Jin Jing
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Fang Weishuo
Department of Natural Products Chemistry, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Lang Liwei
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Zhu Zhixiang
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Chen Xiaoguang
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Zhou Qing
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
-
Li Yan
Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
関連論文
- NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro
- Gradient decrement of annealing time can improve PCR with fluorescent-labeled primers(METHODS)
- Force Microscopy Imaging of Rest Atom on Si(111)7×7 Surface under Strong Tip-Surface Interaction(Condensed matter: structure and mechanical and thermal properties)
- Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome
- A New Enzyme Immunoassay for Aconitine and Its Application to Quantitative Determination of Aconitine Levels in Plasma(Pharmacognosy)
- Electrochemical Energy Generation and Storage : Fuel Cells and Lithium-Ion Batteries
- Protective effect of bicyclol on liver injury induced by hepatic warm ischemia/reperfusion in rats
- Further Study on the Effects of Specimen Thickness and Grain Size on the Creep Behavior of Aluminum Alloy Foils
- Association of Ala589Ser polymorphism of WNK4 gene with essential hypertension in a high-risk Chinese population
- Neurotrophic and growth factor gene expression profiling of mouse bone marrow stromal cells induced by ischemic brain extracts
- Cardiac Functional Analysis by Electrocardiography, Echocardiography and in situ Hemodynamics in Streptozotocin-Induced Diabetic Mice
- Interaction between Serotonin 2A Receptor and Endothelin-1 Variants in Association with Hypertension in Japanese
- Xanthone Derivatives from Swertia kouitchensis
- An in vivo approach for Arabidopsis as a model system for cell biology focused on intracellular trafficking
- Association of Dopamine β-Hydroxylase Polymorphism with Hypertension through Interaction with Fasting Plasma Glucose in Japanese
- Association of a GNAS1 Gene Variant with Hypertension and Diabetes Mellitus
- Endothelin signaling axis activates osteopontin expression through PI3 kinase pathway in A375 melanoma cells
- Expression of GLUT-1 in psoriasis and the relationship between GLUT-1 upregulation induced by hypoxia and proliferation of keratinocyte growth
- Growth Hormone Releasing Peptide-2, a Ghrelin Agonist, Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Rats
- Cardioprotective Effect of Orally Administered Angiotensin-Converting Enzyme Inhibitor Against Ischemia : Reperfusion Injury in the Isolated Rat Heart
- Breast-feeding in Bangkok, Thailand: Current status, maternal knowledge, attitude and social support
- Ischemic rat brain extracts induce human marrow stromal cell growth factor production
- Prevalence and correlates of malnutrition among children in rural minority areas of China
- Surface Plasmon Resonance Immunosensor for IgE Analysis Using Two Types of Anti-IgE Antibodies with Different Active Recognition Sites
- Nicorandil Pretreatment and Improved Myocardial Protection During Cold Blood Cardioplegia
- Quantitative determination of apigenin and its metabolism in rat plasma after intravenous bolus administration by HPLC coupled with tandem mass spectrometry
- Jet ejection from droplets near the Leidenfrost temperature
- An experimental investigation of flow-induced acoustic resonance and flow field in a closed side branch system using a high time-resolved PIV technique
- Generation of Debris in Water-Assisted Femtosecond Laser Drilling of Silica Glass
- Characterization of Micro-Channels Fabricated by In-Water Ablation of Femtosecond Laser Pulses
- P-26 The Studies of Humoral Immunity in Rabbits Vaccinated with Ultraviolet-Attenuated Cercariae of Schistosoma japomicum
- Analysis of intracellular nucleoside triphosphate levels in normal and tumor cell lines by high-performance liquid chromatography
- Active Contour Model Based on Salient Boundary Point Image for Object Contour Detection in Natural Image
- Allergen-driven limiting dilution analysis of human IL-4 and IFN-γ production in allergic rhinitis and clinically tolerant individuals
- Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients
- A Chinese homozygote of familial hypercholesterolemia: identification of a novel C263R mutation in the LDL receptor gene
- A Sensitive Label-free Amperometric CEA Immunosensor Based on Graphene-Nafion Nanocomposite Film as an Enhanced Sensing Platform
- The Expression of SOX9 and Type II Collagen in Condylar Cartilage of Adult Rat after Increasing OVD
- A sensitive LC-MS/MS method for determination of levamisole in human plasma : Application to pharmacokinetic study
- Xanthone Derivatives from Swertia kouitchensis
- Atomic-Scale Imaging of B/Si(111)$\sqrt{3}{\times}\sqrt{3}$ Surface by Noncontact Atomic Force Microscopy
- Expression and Characterisation of the Heavy Chain of Tetanus Toxin : Reconstiution of the Fully-Recombinant Dichain Protein in Active Form
- Induction of Apoptosis by Icariside II through Extrinsic and Intrinsic Signaling Pathways in Human Breast Cancer MCF7 Cells
- Force Mapping of the NaCl(100)/Cu(111) Surface by Atomic Force Microscopy at 78 K
- Lx2-32c, a Novel Taxane Derivative, Exerts Anti-resistance Activity by Initiating Intrinsic Apoptosis Pathway in Vitro and Inhibits the Growth of Resistant Tumor in Vivo
- High-Sensitivity Force Detection by Phase-Modulation Atomic Force Microscopy
- Structure and Deposition Mechanism of 10-Undecenoic Acid Self-Assembled Layers on H-Si (111) Surfaces Studied by Atomic Force Microscopy and Fourier-Transform Infrared
- Induction of Apoptosis by Icariside II through Extrinsic and Intrinsic Signaling Pathways in Human Breast Cancer MCF7 Cells
- High-Speed Phase-Modulation Atomic Force Microscopy in Constant-Amplitude Mode Capable of Simultaneous Measurement of Topography and Energy Dissipation
- Effect of Surface Stress around the SA Step of Si(001) on the Dimer Structure Determined by Noncontact Atomic Force Microscopy at 5 K
- PJS, a novel isocoumarin with hexahydropyrimidine ring from Bacillus subtilis PJS
- NDRG2 in rat liver regeneration : Role in proliferation and apoptosis