PENGARUH Alpinia galanga (LENGKUAS) TERHADAP AKTIVITAS PROLIFERASI SEL DAN INDEKS APOPTOSIS PADA ADENOKARSINOMA MAMMA MENCIT C3 33HH THE EFFECTS OF Alpinia galanga (LENGKUAS) ON THE CELL PROLIFERATION ACTIVITIES AND APOPTOTIC INDEX OF BREAST ADENOCARCINOMA C3 33HH MMI IICCE

Abstract

ABSTRAK Latar belakang: Gangguan keseimbangan antara proliferasi dan apoptosis menyebabkan perkembangan dan progresi tumor. Lengkuas (Alpinia galanga (L.) Willd) mengandung 1’ acetoxy chavicol acetate (ACA). Penelitian terdahulu ACA menunjukan sebagai antikanker, melalui anti inflamasi, menginduksi apoptosis dan menghambat aktivitas proliferasi. Tujuan penelitian untuk membuktikan pengaruh dosis bertingkat ekstrak Alpinia galanga terhadap aktivitas proliferasi dan indeks apoptosis adenokarsinoma mamma. Metode : Penelitian eksperimental hewan coba, dengan desain randomized post test only control group. Sampel 28 ekor mencit C3H yang diinokulasi tumor, dibagi 4 kelompok: kelompok kontrol dan tiga kelompok perlakuan yang diberi ekstrak Alpinia galanga dosis bertingkat (225 mg/KgBB/hari, 450 mg KgBB/hari , 750 mgKg BB/hari) selama 2 minggu. Tumor dilakukan pemeriksaan aktivitas proliferasi dan indeks apoptosis. Indeks apoptosis dievaluasi dengan metode TUNEL. Aktivitas proliferasi dievaluasi dengan menggunakan Allred scoring dengan imunohistokimia Ki-67. Analisis statistik dengan uji nonparametrik Kruska- Wallis dilanjutkan uji Mann- Whitney. Hasil: Terdapat perbedaan bermakna aktivitas proliferasi (p=0,017) ketiga kelompok yang diberikan ekstrak Alpinia galanga dibandingkan Kontrol. ( P1=21,71 ± 19,01, P2 =13,17 ± 11,77, P3 = 6,71 ± 10,87, K=37,43 ± 15,49) Penghambatan aktivitas proliferasi dimulai pada dosis 450mg/kgBB/hari, peningkatan dosis diikuti penurunan aktivitas proliferasi. Terdapat perbedaan bermakna indeks apoptosis (p=0,011) pada ketiga kelompok yang diberikan ekstrak Alpinia galanga dibandingkan kontrol. (P1= 2,70 ± 1,81, P2 = 1,17 ± 1,08, P3= 1,07 ± 1,44). Induksi apoptosis dimulai pada dosis 225 mg/KgBB/hari. Peningkatan dosis tidak diikuti peningkatan indeks apoptosis. Tiga belas ekor mencit mati, maka dilakukan analisa penyebab kematian, didapatkan toksisitas di ginjal. Kesimpulan : Pemberian ekstrak Alpinia galanga dapat menginduksi apoptosis dan menurunkan aktivitas proliferasi. Kata kunci : Alpinia galanga, proliferasi, indeks apoptosis, adenokarsinoma mamma. ABSTRACT Background: The imbalance between apoptosis and cell proliferation may lead to the progression of tumor growth. Lengkuas (Alpinia galanga (L.) Willd) which contain ACA (1’ acetoxy chavicol acetate) had been reported to have anticancer capability on the previous studies through anti inflammation, inducing apoptosis as well as reducing cellular proliferation. The aim of this study is to investigate the effects of Alpinia galanga extract given in gradual dosage on the proliferation activity and apoptotic index of the breast cancer cells. Method : Animal experiment using randomized post test only control group design was done. Twenty-eight C3H mice were inoculated with tumor and were divided into four groups: One control group and three groups administrated by the extract of Alpinia galanga in gradual dosage (225 mg/Kg BW/day, 450 mg/Kg BW/day and 750 mg /Kg BW/day). All of the groups were treated for two weeks. The tumor apoptotic index was evaluated with Tunel method, and the proliferation activities were determined using Allred scoring and Ki-67 immunohistochemical staining. Non parametric Kruskal Wallis continued with Mann-Whitney tests were used to analyze the data. Result : There were significant differences on the proliferation activity (p=0.017) between three groups administered with Alpinia galanga extract compared with control group (P1=21.71 ± 19.01; P2 =13.17 ± 11.77; P3 = 6.71 ± 10.87; K=37.43 ± 15.49) respectively. The disruption of proliferation activity was found on the dosage of 450 mg/Kg BW/day. The increasing dosage was followed by the reduction of proliferation activities. There were significant differences of the apopototic index (p=0.011) of the three groups given Alpinia galanga extract compared with control group (P1= 2.70 ± 1.81; P2 = 1.17 ± 1.08; P3= 1.07 ± 1.44) respectively. The induction of apoptotic index was started on the dosage of 225 mg/Kg BW/day. Increasing of the dosage was not followed by increasing apoptotic index. Thirteen mice were dead and suggested due to nephrotoxicity. Conclution: Alpinia galanga extract can induce apoptotic index and reduce proliferation activities. Keywords : Alpinia galanga, proliferation, apoptotic index, adenocarcinoma of the breast.