Background: Oxicams are non-steroidal anti-inflammatory drugs (NSAIDs). Antitumor potential of NSAIDs has often been reported in literature. We studied antitumor activity of newly synthesized oxicam derivatives (PR17 and PR18) against doxorubicin-sensitive and resistant human colorectal adenocarcinoma cells (LoVo and LoVo/Dx).
Materials and methods: The cytotoxicity of oxicam derivatives alone and in combination with doxorubicin was assessed. Inhibition of P-glycoprotein (ABCB1) transport activity was monitored by flow cytometry. Expression of ABCB1 gene was analyzed by semi-quantitative reverse transcription PCR, while ABCB1 protein expression was assessed by western blotting.
Results: Oxicam derivative PR18 was more cytotoxic to cancer cells than PR17. PR18 was observed to sensitize LoVo/Dx cells to doxorubicin and was identified as an effective multidrug resistance modulator. Additionally, ABCB1 expression was reduced in the presence of PR18.
Conclusion: PR18 was identified as an effective modulator in LoVo/Dx resistant human colorectal adenocarcinoma cells which overexpressed ABCB1 efflux pump.
Keywords: Multidrug resistance (MDR); P-glycoprotein; cyclooxygenase 2 (COX2); non-steroidal anti-inflammatory drugs (NSAIDs).
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.