Electronic Theses and Dissertation

Kanker ovarium merupakan jenis kanker ginekologi ketiga paling umum pada wanita di Indonesia. Pada tahun 2020, tercatat 14.896 kasus baru dengan jumlah 9.581 kematian di Indonesia dan semakin meningkat pada tahun 2022 dengan 15.130 kasus baru dan 9.673 kematian. Akibat pertumbuhan kanker tanpa disertai keluhan spesifik mengakibatkan sulitnya deteksi dini kanker ovarium yang menjadikan angka kematian kanker ovarium tinggi sehingga sering disebut sebagai The Silent Killer. Kemoterapi merupakan modalitas terapi utama karsinoma ovarium dengan stadium lanjut setelah dilakukan pembedahan. P53, VEGF dan COX-2 merupakan ekspresi gen yang berperan dalam proses anti-apoptosis, angiogenesis dan inflamasi, gen tersebut sering ditemukan pada kanker ovarium akibat hasil mutasi dan overekspresi gen. Paclitaxel merupakan regimen kemoterapi yang dipakai dalam kemoresistensi pada sel kanker. Curcumin adalah suatu metabolit yang merupakan suatu bahan alami yang diyakini memiliki efek potensial dalam hal terapi, termasuk sebagai antioksidan, anti-inflamasi, anti-infeksi dan anti-fibrotik. Oleh karena itu interaksi kombinasi paclitaxel dengan curcumin dianggap memegang peranan penting dalam menekan resisten dan meningkatkan apoptosis sel tumor ovarium ganas. Tujuan penelitian ini adalah menganalisa ekspresi gen P53, VEGF dan COX-2 dengan RT-PCR dan mangamati interaksi molekuler terapi kombinasi carboplatin paclitaxel-curcumin secara in silico. Penelitian ini menggunakan blok parafin pasien yang memiliki sel tumor ovarium selama periode tahun 2018-2020 dari Departemen Patologi Anatomi RSUD Dr.Zainoel Abidin. Sebanyak 34 sampel didapatkan yang terdiri atas 17 sel tumor ovarium jinak dan 17 sel tumor ovarium ganas. Dari hasil peneltian ditemukan ekspresi gen P53 pada tumor ganas lebih tinggi ( 1.91 ± 375.21) dari pada ekspresi gen P53 pada tumor jinak (0.16 ± 7.15) dengan hasil uji T pada memperlihatkan perbedaan yang sugnifikan ( p0.05) dengan rerata tumor ovarium ganas (0.18 ± 7.60) lebih tinggi dibandingkan dengan tumor ovarium jinak (0.11 ± 9.58). Sementara itu, ekspresi gen COX-2 pada tumor ovarium ganas (0.38 ± 26.38) lebih tinggi dari pada pada tumor ovarium jinak (0.03 ± 21.38) dengan P

Ovarian cancer ranks as the third most common gynecological malignancy among women in Indonesia. In 2020, 14,896 new cases were reported, leading to 9,581 deaths. By 2022, these figures rose to 15,130 new cases and 9,673 fatalities. The asymptomatic progression of ovarian cancer often delays early diagnosis, earning it the moniker "The Silent Killer." Advanced-stage ovarian carcinoma is primarily treated with chemotherapy following surgical intervention. Mutations and overexpression of critical genes like P53, VEGF, and COX-2—which regulate anti-apoptosis, angiogenesis, and inflammation—are frequently observed in ovarian cancer. Chemotherapy regimens typically include carboplatin and paclitaxel to address chemoresistance. Curcumin, a natural compound, is known for its multifaceted therapeutic properties, including antioxidant, anti-inflammatory, anti-infective, anti-fibrotic, and tumor inhibiting effects. Consequently, the combination of paclitaxel with curcumin potentially reduces resistance and promotes apoptosis in malignant ovarian tumor cells. This study investigates the therapeutic efficacy of combining paclitaxel with curcumin by analyzing the expression of P53, VEGF, and COX-2 genes through RT-PCR. Additionally, it explores the molecular interactions of this combination using in-silico analysis. For this purpose, paraffin-embedded tissue samples from ovarian tumor patients were collected from the Department of Anatomical Pathology at Dr. Zainoel Abidin Hospital between 2018 and 2020. A total of 34 samples were analyzed, comprising 17 benign and 17 malignant ovarian tumor samples. The findings revealed significantly higher P53 gene expression in malignant tumors (1.91 ± 375.21) compared to benign tumors (0.16 ± 7.15), with a statistically significant difference (p < 0.05). Although VEGF gene expression was higher in malignant tumors (0.18 ± 7.60) compared to benign tumors (0.11 ± 9.58), the difference was not statistically significant (p > 0.05). COX-2 gene expression was also notably elevated in malignant tumors (0.38 ± 26.38) versus benign tumors (0.03 ± 21.38), with a significant difference (p < 0.05). In-silico analysis demonstrated that curcumin and its metabolites strongly interact with various anticancer receptor target proteins. Furthermore, curcumin and its derivatives were found to enhance the interaction strength of paclitaxel with these receptors. According to quantitative structure-activity relationship (QSAR) analysis, curcumin is predicted to increase the expression of wild-type P53, while molecular docking suggests it may inhibit the degradation of wild-type P53. Keywords: Ovarian Cancer, P53, VEGF, COX-2, RT-PCR, Paclitaxel, Curcumin, In-silico