6.0; San Diego, CA, USA). 2.6. A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 colorectal cancer (CRC) cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. Conclusion These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins suggested that death rates decreased with aspirin usage for colorectal, stomach and oesophageal cancer in comparison to other cancers [6]. Funkhouser and Sharp, and Farrow found that aspirin users were at a significantly decreased risk from OC [7, 8]. In addition, in a meta-analysis study based on exposure type, aspirin usage was found to have greater protective effect than non-aspirin NSAIDs T56-LIMKi against the development of OC [9], but any use was protective against both histological types (ADC: OR=0.67 and SCC: OR=0.58]. Two more recent meta-analyses lend credence to the protective nature of regular aspirin use: Bosetti estimates a statistically significant reduced relative risk of 0.64 for squamous cell oesophageal cancer [10], and Cuzick report a best estimate risk ratio of 0.7 for incidence and 0.5 for mortality for OC [11]. Barretts oesophagus patients also using NSAIDs exhibit a significantly reduced risk of developing oesophageal ADC (6.6%) compared to non-users (14.3%) [12]. It has been suggested that the reduced cancer risk in BO patients using NSAIDs could be a consequence of a decreased rate T56-LIMKi of acquisition of somatic genomic abnormalities [13], an intriguing finding given that inflammation and genetic instability is intimately linked (expression [33] and mTOR inhibition and activation of AMP-activated protein kinase [34, 35]. Aspirin usage a diagnosis of colon cancer also has a positive outcome: longer survival is noted among patients with mutatedcolorectal cancer, but not with wild type cancer [36]. Taken together, these observations suggest that aspirin can act pleiotropically. We have identified aspirin analogues that are more potent than aspirin with respect to inhibition of colorectal cancer cell line growth and This was T56-LIMKi prepared in an analogous way to PN508 [37] using adipoyl chloride in lieu of succinyl chloride. The off-white solid had a melting range of 174 -176oC ARPC1B (lit.,171-174oC [39]). These carbonate esters were prepared by a variation of the general method for the T56-LIMKi synthesis of alkanoylsalicylate analogues according to Deb test, p 0.01. n.d. = not determined. 2.4. Cell Culture The human oesophageal cancer cell lines and primary oral keratinocyte NOK2101cell line were obtained from Mr Tim Underwood (University of Southampton). The OC cell lines OE21 (of SCC origin) and OE33 (of ADC origin) [40] were cultured in RPMI-1640 medium with L-glutamine supplemented with 10% (v/v) heat inactivated FBS and penicillin-streptomycin. The Flo-1 OC cell line (of ADC origin) [41] was cultured in DMEM medium with L-glutamine supplemented with 10% heat inactivated FBS and penicillin-streptomycin solution. The primary keratinocyte cells, NOK2101 were maintained in EpiCM medium supplemented with 10% FBS and penicillin-streptomycin solution. The SW480 colon adenocarcinoma cell line (ECACC, Salisbury, UK) was cultured in Leibovitz L-15 medium (Thermo Fisher Scientific) containing 10% (v/v) FBS supplemented with L-glutamine-penicillin-streptomycin in sealed culture flasks. The cells were cultured at 37oC in a humidified incubator with 5% CO2 and regularly passaged at ~80% confluency. 2.5. Anti-proliferative Potency of Compounds The cytotoxic effect of aspirin analogues on the oesophageal cancer cells and the non-cancerous keratinocyte cell line was tested using the.