FOLFIRINOX Bileşenlerinin Pankreas Adenokarsinom Hücreleri Üzerindeki Etkileri

Abstract

Pankreatik adenokarsinoma tüm dünyada en ölümcül kanser türlerinden biridir. Bu çalışma, FOLFIRINOX bileşiklerinin (oksaliplatin (OXA), irinotekan (IRI), fluorourasil (5FU) ve leucovorin (LEU)) tekli ve toplu olarak pankreas adenokarsinom hücre hattı (PANC-1) üzerindeki etkilerini hücre canlılığı ve apoptoz için araştırmayı amaçlamıştır. Hücre canlılığı, MTT reaktifi kullanılarak belirlendi ve apoptoz, propidium iyodür – Hoechst 33342 boyama testi kullanılarak değerlendirildi.
Hücre canlılığı sonuçları, FOLFIRINOX uygulamasının diğer test gruplarına kıyasla en yüksek toksisite oranına sahip olduğunu göstermiştir. Ancak apoptotik eğilim kontrol grubundan farklı bulunmadı. Ek olarak, 5FU tekil uygulamada diğer tekil ilaç uygulamalarına nazaran en yüksek toksisiteyi göstermiştir, fakat apoptotik indeksi kontrol grubundan ve FOLFIRINOX tedavisinden farklı bulunmamıştır. Genel olarak, çalışma sonuçları, tedavi rejiminin pankreas adenokarsinom hücre dizileri üzerinde etkili olduğunu gösterdi. Gelecekte, FOLFIRINOX ve 5FU tedavisi lokal pankreas adenokarsinomu tedavilerine uyarlanabilir, ancak pankreas adenokarsinomunun mikroçevresi, doğası gereği pek çok bilinmeyeni barındırdığından, bu lokalize ilaç salım platformlarının geliştirilmesi daha fazla dikkat gerektirmektedir.

Keywords

• FOLFIRINOX; PANC-1 hücreleri; Pankreatik Adenokarsinoma; Sitotoksisite; Apoptoz.

Effects of FOLFIRINOX Components on Pancreatic Adenocarcinoma Cells

Abstract

Pancreatic adenocarcinoma is one of the lethal types of cancer worldwide. This study aimed to evaluate the cytotoxic effects of FOLFIRINOX compounds [oxaliplatin (OXA), irinotecan (IRI), fluorouracil (5FU), and leucovorin (LEU)] on a pancreatic adenocarcinoma cell line (PANC-1), both individually and collectively. Cell viability was determined using the colorimetric MTT reagent and apoptosis was assessed using the propidium iodide – Hoechst 33342 staining assay.
Based on cell viability data, 5FU and FOLFIRINOX treatments were more potent against PANC-1 than the other test groups. The apoptotic trend, nevertheless, was not different between them and the control group. Moreover, OXA, LEU, and IRI significantly increase apoptotic cell death. Our findings indicate that 5FU and FOLFIRINOX are comparably effective in reducing the PANC-1 cell viability. In the future, 5FU and FOLFIRINOX may be adapted to local pancreatic adenocarcinoma treatments, but the development of these localized drug release platforms requires further attention as the microenvironment of pancreatic adenocarcinoma inherently contains many unknowns.         

Keywords

• FOLFIRINOX
• PANC-1 cells
• Pancreatic adenocarcinoma
• Cytotoxicity
• Apoptosis

References

1. [1] Schima, W., Ba-Ssalamah, A., Kölblinger, C., Kulinna-Cosentini, C., Andreas Puespoek, A., Götzinger, P., Pancreatic adenocarcinoma, European Radiology, 17, 638-649, 2007.
2. [2] Rhee, H., Park, M.S., The role of imaging in current treatment strategies for pancreatic adenocarcinoma, Korean Journal of Radiology, 22, 23-40, 2021.2021.
3. [3] Vaccaro, V., Sperduti, I., Milella, M., FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer, New England Journal of Medicine, 365, 768-769, 2011.
4. [4] Zoetemelk, M., Ramzy, G.M., Rausch, M., Nowak-Sliwinska, P., Drug-drug interactions of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin and its activity in colorectal carcinoma treatment, Molecules, 25, 1-20, 2020.
5. [5] Kim, J.H., Lee, S., Oh, S.Y., Song, S., Lee, N., Nam, E.M., Lee, S., Hwang, I.G., Lee, H. R., Lee, K.T., Bae, S., Kim, H.J., Jang, J.S., Lim, D.H., Lee, H.W., Kang, S.Y., Kang, J.H., Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study, Cancer Communications, 38, 1-8, 2018.
6. [6] Auclin, E., Marthey, L., Abdallah, R., Mas, L., Francois, E., Saint, A., Cunha, A.S., Vienot, A., Lecomte, T., Hautefeuille, V., Fouchardière, C., Sarabi, M., Ksontini, F., Forestier, J., Coriat, R., Fabiano, E., Leroy, F., Williet, N., Bachet, J., Tougeron, D., Taieb, J., Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort, British Journal of Cancer, 124, 1941-1948, 2021.
7. [7] Sadeghi, S., Davoodvandi, A., Pourhanifeh, M.H., Sharifi, N., Nezhad, R.A., Sahebnasagh, R., Moghadam, S.A., Sahebkar, A., Mirzaei, H., Anti-cancer effects of cinnamon: Insights into its apoptosis effects. European Journal of Medicinal Chemistry, 178, 131-140, 2019.
8. [8] Tong, H.X., Zhu, F., Biyuan, L., Tao, L., The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis, Scientific Reports, 8, 1-8, 2018.

9. [9] Gil-Ad, I., Shtaif, B., Levkovitz, Y., Nordenberg, J., Taler, M., Korov, I, Weizman, A., Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth. Oncology Reports, 15, 107-112, 2006.
10. [10] Ma, L., Wei, J., Su, G.H., Lin, J., Dasatinib can enhance paclitaxel and gemcitabine inhibitory activity in human pancreatic cancer cells, Cancer Biology & Therapy, 20, 855-865, 2019.
11. [11] Byrne, J.D., Jajja, M.R.N., Schorzman, A.N., Keeler, A.W., Luft, J.C., Zamboni, W.C., DeSimone, J.M.,Yeh, J.J., Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma, Proceedings of the National Academy of Sciences of the United States of America, 113, 2200-2205, 2016.