Peran Siklooksigenase dalam Pertumbuhan Kanker Leher Rahim

Abstract

Ekspresi dan penghambat selektif siklooksigenase-2 (COX-2), seperti selekoksib yang telah dipakai luas sebagai antiinflamasi, diketahui berperan pada kanker dengan menghambat proliferasi dan pertumbuhan tumor serta meningkatkan apoptosis. Tujuan penelitian ini untuk mengetahui pengaruh penghambat COX-2 selektif dan peran COX-2 pada pertumbuhan tumor. Metode penelitian adalah uji eksperimental dengan pretest-posttest control group design yang dilakukan di Rumah Sakit Hasan Sadikin Bandung, November 2007–Oktober 2008. Dua puluh pasien diberi penghambat selektif COX-2 serta kemoradiasi dan 21 pasien mendapat kemoradiasi saja. Dilakukan pemeriksaan COX-2, Ki-67, kaspase-3 secara imunohistokimia, serta ukuran serviks dengan USG transabdominal, praradiasi dan pascaradiasi. Data dianalisis dengan tes Wilcoxon dan korelasi Pearson. Penghambat COX-2 selektif mengakibatkan penurunan sangat bermakna tingkat ekspresi COX-2, yaitu 10% pada kelompok kontrol dan 42% pada kelompok perlakuan (p=0,001), serta ekspresi Ki-67 sebagai penanda proliferasi sebanyak 48% dan -3% pada kelompok kontrol (p=0,007). Tingkat ekspresi kaspase-3 sebagai penanda apoptosis meningkat dengan pemberian penghambat COX-2 selektif sebesar -59% dan 16% pada kelompok kontrol (p<0,001). Penghambat COX-2 selektif juga menyebabkan bertambahnya pengecilan tumor, yaitu: 88% dibandingkan dengan 83% pada kelompok kontrol (p<0,001). Simpulan, COX-2 berperan dalam kanker leher rahim dan penghambat COX-2 selektif menurunkan proliferasi dan meningkatkan apoptosis, sehingga terjadi pengecilan tumor. [MKB. 2010;42(4):169–74].

Kata kunci: Apoptosis, COX-2, kanker leher rahim, penghambat COX2 selektif, pertumbuhan tumor

Role of Cyclooxygenase on Cervical Cancer Growth

Cyclooxygenase-2 (COX-2) expression and selective COX-2 inhibitor such as celecoxib, which widely used as antiinflamatory drug, is known to have role in cancer by reducing proliferation and growth of tumor cells, and increasing apoptosis. The research aims were to investigate the effect of selective COX-2 inhibitor and role of COX-2 on tumor growth. This was an experimental study with pretest-posttest control group design. This study was done at Hasan Sadikin Hospital Bandung, November 2007–October 2008. Twenty patients received selective COX-2 inhibitor and chemoradiation, whereas 21 patients were treated by chemoradiation only, as control group. COX-2, Ki-67, and caspase-3 expression was analyzed by immunohistochemistry. Cervical size was measured by transabdominal ultrasonograpy. All variables obtained before and after external chemoradiation. Data were analyzed using Wilcoxon and Pearson's correlation test. Selective COX-2 inhibitor significantly reduced COX-2 expression, 10% in control group and 42% in treated group (p=0.001) as well as Ki-67 expression as proliferation marker, -3% in the control group and 48% in the treated group (p=0.007). Caspase-3 expression as marker of apoptosis was increased after selective COX-2 inhibitor treatment, 59% whereas only 16% in the control group (p<0.001). In addition, selective COX-2 inhibitor enhanced tumor reduction, 88%versus 83% in control group (p<0.001). In conclusion, COX-2 plays role in uterine cervical cancer and selective COX-2 inhibitor reduced proliferation and increased apoptosis which leads to reduction in tumor size. [MKB. 2010;42(4):169–74].

Key words: Apoptosis, cervical cancer, COX-2, proliferation, selective inhibitor COX2, tumor growth

DOI: http://dx.doi.org/10.15395/mkb.v42n4.31