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HIF-1 and autophagy and chemoresistance

Hui-Mei Wu, Zi-Feng Jiang, Pei-Shan Ding, Li-Jie Shao, Rong-Yu Liu
Hypoxia which commonly exists in solid tumors, leads to cancer cells chemoresistance via provoking adaptive responses including autophagy. Therefore, we sought to evaluate the role of autophagy and hypoxia as well as the underlying mechanism in the cisplatin resistance of lung cancer cells. Our study demonstrated that hypoxia significantly protected A549 and SPC-A1 cells from cisplatin-induced cell death in a Hif-1α- and Hif-2α-dependent manner. Moreover, compared with normoxia, cisplatin-induced apoptosis under hypoxia was markedly reduced...
2015: Scientific Reports
Carolina Simioni, Alice Cani, Alberto M Martelli, Giorgio Zauli, Ayman A M Alameen, Simona Ultimo, Giovanna Tabellini, James A McCubrey, Silvano Capitani, Luca M Neri
Hepatocellular carcinoma (HCC) is one of the most common lethal human malignancies worldwide and its advanced status is frequently resistant to conventional chemotherapeutic agents and radiation. We evaluated the cytotoxic effect of the orally bioavailable dual PI3K/mTOR inhibitor, NVP-BGT226, on a panel of HCC cell lines, since hyperactivated PI3K/Akt/mTOR signaling pathway could represent a biomolecular target for Small Inhibitor Molecules in this neoplasia. We analyzed the drug activity in both normoxia and hypoxia conditions, the latter playing often a relevant role in the induction of chemoresistance and angiogenesis...
July 10, 2015: Oncotarget
Nadine Rohwer, Thorsten Cramer
Resistance towards chemotherapy, either primary or acquired, represents a major obstacle in clinical oncology. Three basic categories underlie most cases of chemotherapy failure: Inadequate pharmacokinetic properties of the drug, tumor cell intrinsic factors such as the expression of drug efflux pumps and tumor cell extrinsic conditions present in the tumor microenvironment, characterized by such hostile conditions as hypoxia, acidosis, nutrient starvation and increased interstitial pressure. Tumor hypoxia has been known to negatively affect therapy outcome for decades...
June 2011: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
E Kirches, M Warich-Kirches
Gliomas of astrocytic origin show only a limited chemotherapy response. Chemoresistance is most pronounced in glioblastoma multiforme, the most common and most malignant glioma, with median survival times not much longer than one year. Failure of chemotherapy partly relies on protective mechanisms against the commonly used DNA alkylating agents, but also on the constitutive activation of the pro-survival PI3K-Akt pathway in glioma cells, which inhibits apoptosis. Therefore, new drugs with an alternative mechanism, independent of DNA alkylation, are required...
January 2009: Anti-cancer Agents in Medicinal Chemistry
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