P19 Cysthionine-β-synthetase inhibition in combination with standard-chemotherapy decreases colorectal cancer metastasis to the liver

Over two-thirds of colorectal cancer patients will develop liver metastases. The current standard-of-care is treatment with the chemotherapeutic agents 5-flurouracil alone or in combination with oxaliplatin (OX) or irinotecan; however, these drugs are often ineffective. We have previously demonstrated that CBS is selectively upregulated in colorectal cancer cells and stimulates hydrogen sulfide (H 2 S)-mediated cell migration and invasion in vitro , processes that define the metastatic phenotype. The aim of this study was to evaluate whether CBS inhibition with aminooxyacetic acid (AOAA) alone or in combination with OX reduced liver metastases in vivo . Human HCT116 colon cancer cells, which express high levels of CBS, were transfected with a luciferase reporter gene. Cells were injected into the cecal submucosa of athymic nude mice. Mice were treated either with vehicle, AOAA (SQ QOD at 9 mg/kg), OX (IP Qwk at 10 mg/kg) or AOAA plus OX (N = 6 per group) for 3 weeks. In vivo metastasis was measured (photons/s) using the IVIS Spectrum Imaging System. Post-harvest, liver metastases were visually counted on serial H& E stained sections and quantified using a weighted scale based on the number of cells within each metastatic focus. In vivo imaging revealed a significant decrease in luciferase activity in the AOAA plus OX group when compared to either AOAA or OX alone ( p = 0.04 and 0.008, respectively). Histological quantification of liver metastasis confirmed the in vivo findings. In conclusion, our data indicate that CBS inhibition enhances the efficacy of OX in reducing metastatic tumor burden.