Abstract
Despite development of numerous target drugs, cancer drug resistance is still one of major obstacles to disturb anti‐cancer treatment in clinical field. Pim‐1 (Proviral integration site for Moloney murine leukemia virus‐1) kinase originally plays an essential role in cytokine‐induced signal transduction. However, overexpression of Pim‐1, as a proto‐oncogene, is also connected with cell proliferation, survival, and drug resistance. We found that the levels of Pim‐1 and mesenchymal markers in drug‐resistant colon cancer cells were highly expressed. To determine the effect of Pim‐1 on generating the chemoresistant cells, we investigated the influence of Pim‐1 on the expression of multi‐drug resistance gene. Targeted inhibition of Pim‐1 using small interference RNA (siRNA) significantly suppressed the up‐regulation of multiple drug resistance (MDR1), multidrug resistance protein 1 (MRP1), and cancer stem cell markers compared with the control group transfected with control siRNA. Silencing of Pim‐1 in chemoresistant HCT‐116 cells with siRNA resulted in downregulation of glycolysis‐associated enzymes, drug‐resistance related proteins, and a disintegrin and metalloproteinase (ADAM) family proteins. In addition, knockdown of Pim‐1 in OxR‐HCT‐116 cells triggered the ER stress‐mediated apoptosis through the loss of oxaliplatin or 5‐fluorouracil resistance. These finding suggest that Pim‐1‐associated signaling pathway plays a critical role in cancer progression and promoting chemoresistance of colon cancer cells.Support or Funding InformationThis study was supported by the Basic Science Research Program of Ministry of Education (NRF‐2015R1D1A1A01056672) and Ministry of Science, ICT & Future Planning (NRF‐2015R1C1A2A01053732) through the National Research Foundation (NRF) of Republic of Korea.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
