PMC:6365940 / 40057-41488
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6365940","sourcedb":"PMC","sourceid":"6365940","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6365940","text":"Here, we evaluated the effects of digoxin in combination with gemcitabine on reversing the drug resistance of gemcitabine in SW1990/Gem and Panc-1/Gem cells. We found that digoxin could reverse drug resistance of gemcitabine in SW1990/Gem and Panc-1/Gem cells. Recently, digoxin was reported to inhibit HIF-1α protein level in different types of cancer cells including C4-2 prostate cancer cell, MDA-MB-231 breast cancer cell, Hep3B hepatoma cell and A549 lung cancer cell [41], [42], [43], [44]. Moreover, studies have shown that HIF-1α was involved in the process of chemoresistance, and inhibition of HIF-1α will increase the sensitivity of cancer cell to chemotherapeutic drugs [45], [46], [47]. In addition, Lee et al. found that digoxin had a novel function as a phosphatase 2A (PP2A) inhibitor, and enhanced the radiosensitivity of radioresistant NSCLC cells through inhibiting PP2A [48]. These previous studies indicated that digoxin-mediated reversing of gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells might be associated with inhibition of HIF-1α and PP2A. However, we found that SW1990/Gem and Panc-1/Gem cells with Nrf2 knockdown exhibited high sensitivity to gemcitabine and digoxin was unable to further improve sensitivity of these cells to gemcitabine, indicating that digoxin-mediated reversing of gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells was Nrf2 dependent.","tracks":[{"project":"2_test","denotations":[{"id":"30735911-22376255-133473739","span":{"begin":474,"end":476},"obj":"22376255"},{"id":"30735911-22231744-133473740","span":{"begin":480,"end":482},"obj":"22231744"},{"id":"30735911-19020076-133473741","span":{"begin":486,"end":488},"obj":"19020076"},{"id":"30735911-23549264-133473742","span":{"begin":492,"end":494},"obj":"23549264"},{"id":"30735911-28028936-133473743","span":{"begin":683,"end":685},"obj":"28028936"},{"id":"30735911-26717965-133473744","span":{"begin":689,"end":691},"obj":"26717965"},{"id":"30735911-24901645-133473745","span":{"begin":695,"end":697},"obj":"24901645"}],"attributes":[{"subj":"30735911-22376255-133473739","pred":"source","obj":"2_test"},{"subj":"30735911-22231744-133473740","pred":"source","obj":"2_test"},{"subj":"30735911-19020076-133473741","pred":"source","obj":"2_test"},{"subj":"30735911-23549264-133473742","pred":"source","obj":"2_test"},{"subj":"30735911-28028936-133473743","pred":"source","obj":"2_test"},{"subj":"30735911-26717965-133473744","pred":"source","obj":"2_test"},{"subj":"30735911-24901645-133473745","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ecb7","default":true}]}]}}