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Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines
Yang Z.; Tam K.Y.
Source PublicationEuropean Journal of Pharmacology
ISSN18790712 00142999

Glycolysis has been observed as a predominant process for most cancer cells to utilize glucose, which was referred to as “Warburg Effect”. Targeting critical enzymes, such as pyruvate dehydrogenase kinase (PDK) that inversely regulating the process of glycolysis could be a promising approach to work alone or in combination with other treatments for cancer therapy. EGFR inhibitors for Non-Small-Cell Lung Cancer (NSCLC) treatment have been applied for decades in clinical practices with great success, but also their clinical benefits were somewhat hampered by the rising acquired-resistance. Combination drug therapy is an effective strategy to cope with the challenge. In this study, we utilized Dichloroacetate (DCA), a widely regarded PDK inhibitor, together with Erlotinib and Gefitinib, two well-known EGFR inhibitors, and demonstrated that the applications of DCA in combination with either Erlotinib or Gefitinib significantly attenuated the viability of EGFR mutant NSCLC cells (NCI-H1975 and NCI-H1650) in a synergistic manner. This synergistic outcome appears to be a combination effect in promoting apoptosis, rather than co-suppression of either EGFR or PDK signaling pathways. Moreover, we have shown that the combination treatment did not exhibit synergistic effect in other NSCLC cell lines without EGFR mutations (A549 or NCI-H460). Together, these observations suggested that combined targeting of EGFR and PDK in NSCLC cells exerted synergistic effects in an EGFR mutation-dependent fashion.

KeywordDichloroacetate Drug Combination Epidermal Growth Factor Receptor Erlotinib Gefitinib Pyruvate Dehydrogenase Kinase
URLView the original
Indexed BySCIE
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000385327500052
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
AffiliationUniversidade de Macau
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Yang Z.,Tam K.Y.. Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines[J]. European Journal of Pharmacology,2016,789:458-467.
APA Yang Z.,&Tam K.Y..(2016).Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines.European Journal of Pharmacology,789,458-467.
MLA Yang Z.,et al."Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines".European Journal of Pharmacology 789(2016):458-467.
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