Sari, Felita Galih Perwita and Prof. Agustina Tri Endharti, S. Si., Ph.D and Drs. Sofy Permana, M.Sc., D.Sc. (2023) Pengaruh Terapi Kombinasi Bevacizumab dan Ekstrak Jamur Kuping Hitam (Auricularia polytricha) Terhadap Ekspresi microRNA-140 dan Kemampuan Migrasi Pada Sel Kanker Kolorektal In vitro. Magister thesis, Universitas Brawijaya.
Abstract
Kanker kolorektal merupakan keganasan pada kolon serta rektum. Di Indonesia, kanker kolorektal merupakan jenis kanker ketiga terbanyak. miR-140 telah menarik banyak perhatian karena terlibat dalam berbagai perkembangan kanker, termasuk KKR. Ekspresi miR-140 berkurang dalam spesimen KKR dan ekspresi ektopik miR-140 dapat menekan proliferasi sel serta menginduksi siklus sel fase G1 dan G2 yang dimediasi sebagian melalui penurunan regulasi HDAC4 dalam sel KKR. Bevacizumab adalah VEGF inhibitor yang dapat menghambat pembentukan pembuluh darah tumor baru dan mengakibatkan regresi vaskularisasi tumor. Ekstrak polisakarida dan etanol dari Auricularia polytricha dilaporkan memiliki aktivitas antitumor. Jamur ini memiliki banyak efek antikanker, termasuk inaktivasi karsinogen, penghambatan pertumbuhan sel kanker, angiogenesis, dan metastasis. Penelitian ini menggunakan metode true experimental post-test only control group design dengan tujuan untuk mengetahui pengaruh terapi kombinasi bevacizumab dengan ekstrak jamur kuping hitam (Auricularia polytricha) terhadap ekspresi miR-140 dan kemampuan migrasi pada sel kanker kolorektal in vitro Sampel cell line HT-29 diperoleh dari ATCC. Terdapat enam kelompok perlakuan antara lain, satu kelompok diberi terapi tunggal masing-masing yaitu bevacizumab 10 μg/ml dan ekstrak Auricularia polytricha 200 μg/ml, tiga kelompok diberi terapi kombinasi bevacizumab 10 μg/ml dan ekstrak Auricularia polytricha dengan dosis masing-masing 50 μg/ml, 100 μg/ml, 200 μg/ml, dan satu kelompok terakhir tidak diberikan perlakuan. Kemudian dilakukan pengamatan terhadap migrasi sel menggunakan scratch assay dan ekspresi miR-140 menggunakan RT-PCR. Hasil migrasi sel dan ekspresi miR-140 selanjutnya di uji normalitas (Shapiro-Wilk test) dan uji homogenitas (Levene test). Analisis perbedaan antar kelompok perlakuan menggunakan uji One Way ANOVA, kemudian dilakukan analisis post-hoc menggunakan uji Tukey. Hasil penelitian menunjukkan bahwa pemberian ekstrak Auricularia polytricha sebagai terapi kombinasi dengan bevacizumab mampu meningkatkan ekspresi miRNA-140 dan menurunkan kemampuan migrasi sel KKR (HT-29) melalui peningkatan area inhibisi secara in vitro.
English Abstract
Colorectal cancer (CRC) is a malignancy originating from the large intestine, consisting of the colon (the longest part of the large intestine) and/or the rectum (the last small part of the large intestine before the anus). In Indonesia, colorectal cancer is the third most common type of cancer. miR-140 has attracted a lot of attention because it is involved in various cancer developments, including KKR. MiR-140 expression was reduced in KKR specimens and ectopic expression of miR-140 could suppress cell proliferation as well as induce G1 and G2 phase cell cycles mediated in part through downregulation of HDAC4 in CRCcells. Bevacizumab is a VEGF inhibitor that can inhibit the formation of new tumor blood vessels and result in regression of tumor vasculature. Polysaccharide and ethanol extracts from Auricularia polytricha were reported to have antitumor activity. This mushroom has many anticancer effects, including inactivation of carcinogens, inhibition of cancer cell growth, angiogenesis and metastasis. This study used a true experimental post-test only control group design method which aims to determine the effect of combination therapy of bevacizumab with black ear fungus (Auricularia polytricha) extract on migration ability and expression of miR-140 in colorectal cancer cells in vitro. The sample used in this study is the cell line HT-29 obtained from ATCC. There were six treatment groups, one group was given single therapy, namely bevacizumab 10 g/ml and Auricularia polytricha extract 200 g/ml, three groups were given combination therapy with bevacizumab 10 μg/ml and Auricularia polytricha extract with a dose of each 50 μg/ml, 100 μg/ml, 200 μg/ml, and one last group was not given any treatment. Then, the metastases were observed using a scratch assay and miR-140 expression using RT-PCR. The results of metastasis and miR-140 expression were tested for normality (Shapiro-Wilk test) and homogeneity test (Levene test). Analysis of differences between treatment groups used the One Way ANOVA test, then post-hoc analysis was performed using the Tukey test. The results showed that administration of Auricularia polytricha extract as a combination therapy with bevacizumab was able to increase the expression of miRNA-140 and decrease the ability of KKR cell migration (HT-29) by increasing the area of inhibition in vitro.
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | 0423060050 |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.02 Special topics of disease > 616.025 Medical emergencies / Emergency medicine / Emergency nursing / Triage (Medicine) |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | Endang Susworini |
| Date Deposited: | 27 Nov 2023 01:20 |
| Last Modified: | 27 Nov 2023 01:20 |
| URI: | http://repository.ub.ac.id/id/eprint/204646 |
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