Ferit AVCU, Şefik GÜRAN, Ali Uğur URAL, Zehra Dilşad ÇOBAN

Kemoterapotik ajan olarak dosetakselin ARH 77 Ig G plazma hücreli lösemi hücre serisi üzerindeki sitotoksik etkisi

Amaç. Dosetaksel, hücrede mitotik iğciğin oluşum aşamasında mikrotübül stabilizasyonuna nedenolarak hücre bölünmesini durdurup hücrenin apopitozise gidişini sağlar. Dosetaksel meme, prostatve mesane kanserinde sık kullanılan bir ilaçtır. Çalışmada Ig G plazma hücreli lösemi örneği olanhücre hattı [ARH-77 ATCC No: CRL-1621] üzerinde başka birçok kanserin tedavisinde ilaçolarak kullanılan dosetaksel ile ortaya çıkabilecek sitotoksik etki araştırıldı. Yöntem. ÇalışmadaARH-77 hücreleri üzerinde 0,1-1-10-50-100 umol/L olacak şekilde farklı dosetakselkonsantrasyonları kullanılarak sitotoksik etki incelendi. Sitotoksik etki XTT testi iledeğerlendirildi. Bulgular. İnsan Ig G plazma hücreli lösemi örneğini oluşturan ARH-77 hücrehattında dosetakselin artan konsantrasyonlarında oluşturduğu sitotoksik etki ortaya kondu. Sonuç.Veriler dosetakselin 50 umol konsantrasyonunda ARH-77 hücreleri üzerinde letal doza eriştiğinigöstermiştir. Dosetakselin plazma hücreli lösemi hücre hattında etkin sitotoksik etkisi bu ilacınnadir gözlenen ve kötü prognozla karakterize hastalık tedavisinde kullanılabileceğinidüşündürmektedir. Fakat bu ilacın plazma hücreli lösemide kullanımı için daha ileri testlere ihtiyaçvardır.

The cytotoxic effect of docetaxel on Ig G plasma cell leukemia cell line ARH-77 as a chemotherapeutic agent

Aim.: Docetaxel causes microtubule stabilization during mitotic spindle organizing in cell andforces the cell to go apoptosis. Docetaxel is widely used in breast, prostate and bladder cancer. Thepotential cytotoxic effect of docetaxel, a chemotherapeutic agent which is used in various cancers,on Ig G plasma cell leukemia cell line (ARH-77-ATCC No: CRL-1621) was investigated in thisstudy. Methods. The cytotoxic effect of docetaxel on ARH-77 cell line was evaluated at differentconcentrations namely 0.1-1-10-50-100 umol/L by using XTTtest. Result. It was shown that,docetaxel had significant cytotoxic affect at higher concentrations on ARH-77 cell line whichforms a sample of human Ig G plasma cell leukemia. Conclusion. The data represent that thelethal dose of docetaxel in ARH-77 cell line is at the concentration of 50 umol/L. Our resultssuggest that docetaxel could be useful in the treatment of plasma cell leukemia of rare casesassociated with poor prognosis. But further tests are needed to use this drug in plasma cellleukemia.

PDF

___

1. Albarracin F, Fonseca R. Plasma cell leukemia. Blood Rev 2011; 25: 107-12.
2. Sher T, Miller KC, Deeb G, Lee K, Chanan-Khan A. Plasma cell leukaemia and other aggressive plasma cell malignancies. Br J Haematol 2010; 150: 418-27.
3. Morse DL, Gray H, Payne CM, Gillies RJ. Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol Cancer Ther 2005; 4: 1495- 504.
4. Lyseng-Williamson KA, Fenton C. Docetaxel: a review of its use in metastatic breast cancer. Drugs 2005; 65: 2513-31.
5. Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V. Docetaxel vs. vinorelbine in elderly patients with advanced non-small-cell lung cancer: a hellenic oncology research group randomized phase III study. Clin Lung Cancer 2011; 12: 155-60.
6. Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 1992; 10: 334-42.
7. Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 1988; 48: 4827-33.
8. Dönmez Y, Gündüz U. Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells. Biomedicine &Pharmacotherapy 2011; 65: 85-9.
9. Mutlu P, Baran Y, Ural AU, Avcu F, Dirican B, Beyzadeoglu M, Gündüz U. Effect of cobalt-60 (γ radiation) on multidrug-resistant multiple myeloma cell lines. Cell Biology Int 2011; 35: 721-5.
10. Clarke SJ, Rivory LP. Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 1999; 36: 99-114.
11. Morgan C, Lewis PD, Jones RM, Bertelli G, Thomas GA, Leonard RC. The in vitro anti-tumour activity of zoledronic acid and docetaxel at clinically achievable concentrations in prostate cancer. Acta Oncol 2007; 46: 669-77.
12. Fury MG, Pfister DG. Current Recommendations for Systemic Therapy of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer. J Natl Compr Canc Netw 2011; 9: 681-9.
13. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma 2010; 2010: 506182.
14. Fabbri F, Amadori D, Carloni S, Brigliadori G, Tesei A, Ulivi P, Rosetti M, Vannini I, Arienti C, Zoli W, Silvestrini R. Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells. J Cell Physiol 2008; 217: 494-501.
15. Cortes JE, Pazdur R. Dosetaxel. J Clin Oncol 1995; 13: 2643-55.
16. Jimenez-Zepeda VH, Dominguez-Martinez VJ. Plasma cell leukemia: a highly aggressive monoclonal gammopathy with a very poor prognosis. Int J Hematol 2009; 89: 259-68.
17. Uysal Y, Ural AU, Avcu F, Güngör S, Hürmeriç V, Erdem Ü, Durukan AK, Bayer A, Bayraktar MZ. Meme kanseri (MCF-7) ve Burkitt lenfoma (Raji) hücre dizileri üzerine in vitro ortamda hiperisin ile fotodinamik tedavi araştırma sonuçları. Gülhane Tıp Dergisi 2007; 49: 147-52.