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Doxorubicin (DOX) is a first-line chemo drug for cancer therapy, yet it fails to treat multidrug resistant tumors. Hypoxia is a major reason causing failure in chemotherapy. Particularly, hypoxia up-regulates its responsive transcription factor - hypoxia-inducible factors (HIF) to induce the overexpression of drug resistant genes. Metformin (MET) is recently found to cooperate with DOX against multiple tumors. As a mitochondrial inhibitor, MET could suppress tumor oxygen consumption, and thereby modulate hypoxic tumor microenvironment. In this study, we used cationic liposomes to co-deliver both DOX and MET for treating multidrug resistant breast cancer cells - MCF7/ADR. Faster release of MET enhanced cytotoxicity of DOX through attenuating hypoxic stress both in vivo and in vitro. MET reduced the cellular oxygen consumption and inhibit HIF1α and P-glycoprotein (Pgp) expression in vitro. In addition, the dual drug loaded liposomes increased tumor targeting and intratumoral blood oxygen saturation, which suggested that the tumor reoxygenation effect of MET facilitated to exert its synergistic activity with DOX against MCF7/ADR xenografts. In general, our study represents a feasible strategy to boost therapeutic effect in treating multidrug resistant cancer by improving the hypoxic tumor microenvironment.
This article was published in the following journal.
Name: Molecular pharmaceutics
Adenovirus (Ads) is one of the most popular vectors used in gene therapy for the treatment of cancer. However, systemic therapy is limited by circulating antiviral antibodies and poor viral delivery i...
The efficacy of metformin in treating cancer has been extensively investigated since epidemiologic studies associated this anti-diabetic drug with a lower risk of cancer incidence. Since tumors are co...
The therapeutic use of silk-derived materials such as fibroin in biomedicine is well-established in Southeast Asian countries. Studies indicated that silk fibroin (SF) peptide enhances insulin sensiti...
In this study, the modulatory effect of ferulic acid on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) was examined in KB Ch8-5 resistant cells and drug-resistant tumor xenografts. We obser...
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Alzheimer's disease (AD) and other forms of dementia are rapidly increasing with the aging of the population, and show a clear preponderance among people with insulin resistance. Metformin...
Metformin has been used clinically for over 50 years, as a glucose lowering agent. Direct and indirect anti-inflammatory effects of metformin have been reported in animal and clinical stu...
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A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.
Drug formulations or delivery systems intended to discourage the abuse of CONTROLLED SUBSTANCES. These may include physical barriers to prevent chewing or crushing the drug; chemical barriers that prevent extraction of psychoactive ingredients; agonist-antagonist combinations to reduce euphoria associated with abuse; aversion, where controlled substances are combined with others that will produce an unpleasant effect if the patient manipulates the dosage form or exceeds the recommended dose; delivery systems that are resistant to abuse such as implants; or combinations of these methods.
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
A pharmaceutical preparation of sitagliptin phosphate and metformin hydrochloride that is used in the treatment of TYPE 2 DIABETES.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...