Download In vitro evaluation of the synergistic interactions of

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In Vitro Evaluation of the Synergistic Interactions of Oxaliplatin and Gemcitabine in
Bladder Cancer
Aditi Mehta
Mentor: John Fruehauf
Bladder cancer is the fourth leading cause of cancer in men in the United States and is among the top
ten causes of cancer in women. Current treatment for metastatic bladder involves a combination of
cisplatin and gemcitabine. However, the duration of clinical response is 12 to 15 months. Treatment
failure is related to the development of drug resistance to this combination. Platinum drugs work by
forming adducts on the DNA and inhibiting DNA synthesis. Cells can remove these adducts through
use of DNA repair mechanisms. Our hypothesis is that oxaliplatin, a third generation platinum drug,
may be a better choice for combination with gemcitabine, due to its bulky steric diaminocyclohexane
(DACH) group, which may hinder DNA repair mechanisms, thereby making it more effective. We
compared the in-vitro cytotoxic effects of these two agents on the T-24 bladder cancer cell line. Drug
response was determined using the XTT assay, which measures cell viability. We observed that the
50% inhibitory concentrations (IC50) of oxaliplatin and cisplatin alone were 4100 nM and 273 nM
respectively. The IC50 of oxaliplatin with gemcitabine was 2050 nM, while the IC50 of cisplatin with
gemcitabine was 409 nM. These results suggest that more oxaliplatin is needed to provide the same
effect as cisplatin. Both oxaliplatin-gemcitabine and cisplatin-gemcitabine showed antagonistic effects
when assessed for synergy. To further test our hypothesis, the ability of oxaliplatin to bind to DNA
of the T-24 cells and escape the DNA mismatch repair will be compared with cisplatin in future
experiments using Atomic Absorbance Spectroscopy.