Characterisation of Colorectal Cancer Cell Line LoVo and Drug-Adapted LoVo Cell Lines

A major hurdle in cancer treatment is acquired resistance, often rendering previously positive treatments ineffective. One way this hurdle can be jumped is through use of drug combinations, counteracting the chance of treatment failing due to acquired resistance to one drug. It is important to know which drug combinations are effective, as if acquired resistance occurs to one drug, the other will need to remain effective to prevent poor patient outcomes. It is therefore important to know which drugs work well together before resistance is acquired and will continue to do so if the cancer acquires resistance to either drug. During this project, four colorectal cancer cell lines were used, 3 of which were drugadapted. These were: LoVo, LoVor5-FU200ng/ml, LoVorIrino200ng/ml, and LoVorOxali4000ng/ml. These are useful as a model, but there are limitations such as the unlikeness to in vivo models. Growth curve assays were completed to calculate doubling times of each cell line. No significant difference was seen in the doubling times of drug-adapted cell lines compared to the parental LoVo cell line. Cell viability assays were done to show cross-resistance or collateral sensitivity in the drug-adapted cell lines to the drugs being tested (5-FU, irinotecan, oxaliplatin, miyabeacin, I-BET, JQ1, rucaparib, Olaparib, and verapamil) in comparison to the parental LoVo cell line. This assay can show which drugs may be effective in combination, or which may be useful if resistance shows to a certain drug, and conclusions may also be able to be made on the specific mechanism of resistance present in a drug-adapted cell line. The results show that 5-FU and oxaliplatin are likely to be an effective drug combination. Conclusions were also made on the resistance mechanism in LoVorIrino200ng/ml, that perhaps the mechanism is upregulation of ABC transporters (ATP binding cassette transporters). The results can be a platform to test some drugs further and, perhaps after sequencing, determine which drugs would be effective against certain mechanisms of resistance.