title: Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.
abstract: Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Affiliated Hospital of Guizhou Medical University Guiyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors.forename: Wenlei
authors.initials: W
authors.lastname: Zhuo
authors.affiliation: College of Food Science and Nutritional Engineering, China Agriculture University Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Chen
keywords: Erlotinib-resistance; Fisetin; Lung adenocarcinoma; reversion; signaling pathways