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World J Surg Oncol. 2009; 7: 2.
Published online 2009 January 6. doi: 10.1186/1477-7819-7-2.
PMCID: PMC2628910
Does Doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer?
Jayesh Sagar,corresponding author1,2 Kevin Sales,1 Sas Dijk,1 JanWillem Taanman,3 Alexander Seifalian,2 and Mark Winslet1,2
1Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK
2Academic Department of Surgery, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK
3Department of Clinical Neuroscience, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK
corresponding authorCorresponding author.
Jayesh Sagar: jsagar_2001/at/yahoo.com; Kevin Sales: k.sales/at/medsch.ucl.ac.uk; Sas Dijk: s.dijk/at/medsch.ucl.ac.uk; JanWillem Taanman: j.taanman/at/medsch.ucl.ac.uk; Alexander Seifalian: a.seifalian/at/medsch.ucl.ac.uk; Mark Winslet: m.winslet/at/mesch.ucl.ac.uk
Received May 16, 2008; Accepted January 6, 2009.
Abstract

Background
In recent years, apart from antibacterial properties, doxycycline is reported to have cytotoxic and anti-proliferative actions in various cancers including colorectal cancer. Colorectal cancer constitutes one of the most common cancers in the western population. Apart from surgery, chemotherapy plays crucial role in the treatment of colorectal cancer. Cisplatin and oxaliplatin are most commonly used platinum compounds for the cancer chemotherapy. This study has looked for any impact of doxycycline on the cytotoxic effects of platinum compounds in colorectal cancer including its mechanisms of actions.

Methods
HT 29 colorectal cancer cells were used for this study. These cells were treated with cisplatin and oxaliplatin with or without doxycycline treatment. The caspase 3 gene expression was quantitated by gel electrophoresis and qualitated by real time polymerase chain reactions. The caspase 3 activity was assessed in HT 29 cells with fluorescence kit.

Results
The results revealed increased caspase 3 gene expressions and activities in HT 29 cells treated with cisplatin, oxaliplatin and doxycycline; however the combination of doxycycline with cisplatin and oxaliplatin did not report increased caspase 3 gene expressions and activity compared to cisplatin and oxaliplatin alone.

Conclusion
We concluded that doxycycline has role in apoptosis induction in the colorectal cancer. However, it did not show any synergy with platinum compounds in the colorectal cancer cells. This study also pointed towards possible caspase-independent actions of doxycycline with cisplatin and oxaliplatin. However, further work is required to underpin the mechanisms of actions of doxycycline.