Tek bir ajan olarak setuksimab oral kavitekanser hücrelerinde doza bağımlı etkiye sahiptir: Bir in vitro çalışma

Cetuximab alone has a dose-dependent antitumor effect in oral cavity cancer cells: an in vitro study

GÖRKEM ESKİİZMİR,GİZEM ÇALIBAŞI KOÇAL,TUĞBA UYSAL KILIÇ,Hülya ELLİDOKUZ,Yasemin BASKIN

Özet

Amaç: Tek bir ajan olarak setuksimab>n oral kavite kanserlerinin tedavisindeki antitümöral etkisini de¤erlendirmek ve oral kavite yass> epitel hücreli karsinom dizininde (OCSCCCL) doza ba¤>ml> büyü- meyi inhibe etme etkisini aç>kl>¤a kavuflturmak. Yöntem: OCSCCCL (UPCI-SCC131) kültürü elde edildi ve xCELLigence RTCA SP cihaz> kullan>larak izlendi. Daha sonra yedi gruba bölüfltürüldü: (i) negatif kontrol: besiyeri+OCSCCCL, (ii) pozitif kontrol: besiyeri+OCSCCCL+sisplatin 10 ?M/ml, (iii) besiyeri+OCSCCCL+setuksimab 25 ?g/ml, (iv) besiyeri+OCSCCCL+setuksimab 50 ?g/ml, (v) besiyeri+OCSCCCL+setuksimab 100 ?g/ml, (vi) besiyeri+OCSCCCL+setuksimab 200 ?g/ml, (vii) besiyeri+OCSCCCL+setuksimab 400 ?g/ml. Hücre indeksi ve viyabilite istatistiksel aç>dan incelendi ve gruplar aras>nda karfl>laflt>r>ld>. Bulgular: Hücre indeksinin (ortalama de¤er) ve viyabilite yüzdesinin da¤>l>m> flu flekilde bulundu: (i) 2.66 (%100), (ii) 0.17 (%6.08), (iii) 2.28 (%85.71), (iv) 2.31 (%86.84), (v) 1.92 (%72.18), (vi) 1.79 (%67.29), (vii) 0.28 (%10.53). n uyguland>¤> çal>flma gruplar>n>n tümünde istatistiksel aç>dan anlaml> idi (Pillai trasesi; p laflt>r>ld>¤>nda setuksimab>n antitümöral etkisi ilk olarak 100 ?g/mL dozda saptand> (p=0.01). Ancak 10 ?M sisplatinin etkisine istatistiksel aç>dan benzer antitümöral etki için 400 ?g/mL doz gerekliydi. Sonuç: Tek bafl>na setuksimab potansiyel olarak etkili bir kemoterapötik ajan olup OCSCCL'de konsantrasyona ba¤>ml> büyümeyi inhibe edici etkiye sahiptir. Setuksimab>n antitümöral aktivitesi bafllang>ç- ta 100 ?g/mL dozda saptanm>flt>r. Ancak 400 ?g/mL dozda anlaml> bir antitümöral etki belirlenmistir.

Abstract

Objective:To evaluate the antitumor effect of cetuximab as a singleagent for the treatment of oral cavity cancers and to clarify the dosedependent growth inhibitory effect in oral cavity squamous cell carcinoma cell line (OCSCCCL). Methods:The OCSCCCL (UPCI-SCC131) were cultured and continuously monitored using the xCELLigence RTCA SP instrument.Thereafter, they were divided into seven groups as: (i) negative control:medium+OCSCCCL, (ii) positive control: medium+OCSCCCL+cisplatin 10 ?M/ml, (iii) medium+OCSCCCL+cetuximab 25 ?g/ml, (iv)medium+OCSCCCL+cetuximab 50 ?g/ml, (v) medium+OCSCCCL+cetuximab 100 ?g/ml, (vi) medium+OCSCCCL+cetuximab 200 ?g/ml,(vii) medium+OCSCCCL+cetuximab 400 ?g/ml. The cell index andviability were statistically analyzed and compared between groups. Results: The distribution of cell index (mean value) and percentageof viability in groups were as follows: (i) 2.66 (100%), (ii) 0.17(6.08%), (iii) 2.28 (85.71%), (iv) 2.31 (86.84%), (v) 1.92 (72.18%), (vi)1.79 (67.29%), (vii) 0.28 (10.53%). The change trend in drug concentration was statistically different in all study groups to which cetuximab was administered (Pillai's trace; p<0.0001). The antitumor effectof cetuximab was initially detected at a dose of 100 ?g/mL, whencompared with negative control (p=0.01). However, a dose of 400?g/mL was required in order to have a statistically similar antitumoreffect of cisplatin at a dose of 10 ?M. Conclusion:Cetuximab alone is a potentially effective chemotherapeutic agent and has a concentration-dependent growth inhibitoryeffect in OCSCCCL. The antitumor activity of cetuximab was initially detected at a dose of 100 ?g/mL. However, significant antitumoreffect was determined at a dose of 400 ?g/mL.