Evaluation of Cytotoxicity and Cell Morphological Changes by FOLFIRINOX in Pancreatic Cancer Cell Line

Samah, Nazirah (2020) Evaluation of Cytotoxicity and Cell Morphological Changes by FOLFIRINOX in Pancreatic Cancer Cell Line. [Project Paper] (Submitted)

Text FPSK2 2020 23.pdf Download (2MB)

Abstract

FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan and oxaliplatin) is the new first-line drug regimen of chemotherapy in treating pancreatic cancer disease. Patients receiving 400mg/m2 leucovorin, 180mg/m2 irinotecan, 85mg/m2 oxaliplatin and bolus 400mg/m2 5-fluorouracil followed by 2,400mg/m2 over a 46-hours infusion has resulted 11.1 months of overall survival with common unwanted side effects encountered including neutropenia. As it is associated with high toxicity, few different patients-tailored modifications of FOLFIRINOX have been made without prior in vitro testing, resulting in an unknown efficacy. Objective: This study was aimed to determine the cytotoxicity effect and cell morphology changes by FOLFIRINOX, and to determine the best drugs concentration combination in inhibiting Capan-2 cells. Methodology: Identification of the half maximum inhibitory (IC50) of all drugs in FOLFIRINOX at different concentrations (3.125, 6.25, 12.5, 25, 50 and 100uM) against Capan-2 cells were performed. Different concentration combinations of FOLFIRINOX were then generated by performing an orthogonal design in SPSS using a range of IC50 values of each drug. The cytotoxicity, cell morphology changes and drug interaction of the generated drug combinations were confirmed using CCK-8 assay, AO/PI staining and Response Surface Methodology (RSM), respectively. Results: The IC50 of 5-fluorouracil, oxaliplatin, irinotecan and leucovorin are 17.9uM, 16.61uM, 17.38uM and 9.289uM, respectively. Few morphological changes such as chromatin condensation, membrane blebbing and cell fragmentation were observed in FOLFIRINOX treated Capan-2 cells. Among the 9 combinations generated by SPSS, combination of 30uM of 5-fluorouracil, 20uM of oxaliplatin, 1uM of irinotecan and 5uM of leucovorin gave the highest percentage of cell inhibition (62.49%). However, analyses via RSM gave a combination of 1uM of 5-fluorouracil, 1uM of oxaliplatin, 15uM of irinotecan and 10uM leucovorin as the best drugs combination. Conclusions: The modified FOLFIRINOX concentration found in this study differs from standard combination used in pancreatic cancer treatment. Further studies needed to validate the findings by determining the maximum response achievable from the modified FOLFIRINOX in research settings, and the capacity for sufficient therapeutic effect with less occurrence of unwanted side effects in clinical settings.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 07:56
Last Modified:	22 Aug 2023 07:56
URI:	http://psaspb.upm.edu.my/id/eprint/1311

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