OncoTargets and Therapy (Dec 2019)
Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment
Abstract
Xuansheng Ding,* Lei Ge,* Aiwen Yan, Yuyin Ding, Junye Tao, Qianqian Liu, Chen Qiao* Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen QiaoDepartment of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Jiangning District, Nanjing, Jiangsu, People’s Republic of ChinaTel +86 13913807716Email [email protected]: Due to the resistance of cancer cells, chemotherapy has been severely restricted. Docosahexaenoic acid (DHA) has been broadly identified as the chemo-sensitizing agent and revertant of multidrug resistance owing to its pleiotropic characteristics; however, it has not been well interpreted. The purpose of this research was to identify the anticancer role of DHA and its combination with the chemotherapeutic agent Gefitinib in non-small cell lung cancer (NSCLC).Methods: Human chemo-sensitive NSCLC PC-9 cells and the Gefitinib-resistant counterpart PC-9/GR cells were adopted to assess the effects of the integrated DHA and Gefitinib treatments in vitro and vivo, for which the combination index (CI), apoptosis rate and the epithelial growth factor receptor (EGFR) pathway were analyzed.Results: Comparing with the control cells, the DHA-treated PC-9/GR cells triggered the increase of drug absorption and sensitivity, suggesting that the sensitivity of chemotherapeutic drug could be induced by DHA. Moreover, the elevation of phosphorylation levels of EGFR and the downstream extracellular signal-regulated kinase (ERK) in the cellular lysates were induced by the DHA+Gefitinib treatment. Additionally, the long-term Gefitinib stimulated PC-9 model revealed that DHA could revert the Gefitinib resistance.Conclusion: This is the first research that indicated the novel biochemical effect of DHA, which can help in overcoming the resistance of EGFR-TKI in NSCLC cells and broaden the horizon of the DHA supplementation during the NSCLC therapy.Keywords: non-small cell lung cancer, drug resistance, DHA
