Rahmadani, Syakirah Shafwah (2025) Pengaruh Treatment Cisplatin terhadap Jalur Persinyalan cGAS-STING Pada Sel Kanker Kandung Kemih (Lini Sel MB49) dengan Defisiensi ARID1A. Masters thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Defisiensi gen ARID1A merupakan kondisi umum pada berbagai jenis kanker, termasuk kanker kandung kemih, yang menyebabkan gangguan mekanisme perbaikan DNA dan akumulasi DNA sitosolik. Akumulasi ini dapat mengaktivasi jalur imun bawaan cGAS-STING, yang memicu ekspresi gen interferon tipe I dan interferon stimulated genes (ISG). Penelitian ini bertujuan untuk mengevaluasi pengaruh terhadap aktivitas jalur cGAS-STING pada lini sel kanker kandung kemih MB49 dengan defisiensi gen ARID1A. Uji dilakukan menggunakan sel MB49 shARID1A dan shScramble, dengan dan tanpa sifat resisten terhadap cisplatin. Validasi knockdown dilakukan melalui uji qPCR dan western blot analysis, sedangkan sifat resistensi lini sel MB49 dikonfirmasi melalui uji sitotoksisitas. Setelah perlakuan cisplatin, dilakukan analisis ekspresi gen-gen target jalur cGAS-STING seperti IFNB1, ISG15, CCL5, CXCL9, dan CXCL10 menggunakan uji qPCR. Hasil menunjukkan bahwa pemberian cisplatin meningkatkan ekspresi gen-gen tersebut secara signifikan pada sel dengan defisiensi gen ARID1A, yang menunjukkan adanya peningkatan aktivasi jalur cGAS-STING. Hal ini mengindikasikan bahwa cisplatin tidak hanya bersifat sitotoksik tetapi juga mampu memperkuat respon imun antitumor melalui jalur imun bawaan. Adanya anomali respon gen-gen turunan jalur persinyalan cGAS-STING pada lini sel MB49 dengan sifat resistensi terhadap cisplatin memberikan petunjuk untuk dilakukanya uji lanjutan yang dapat meperjelas jalur persinyalan pada lini sel kanker dengan sifat resisten terhadap cisplatin
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ARID1A gene deficiency is a common condition in various types of cancer, including bladder cancer, and is associated with impaired DNA repair mechanisms and the accumulation of cytosolic DNA. This accumulation can activate the innate immune cGAS-STING signaling pathway, which triggers the expression of type I interferon genes and interferon-stimulated genes (ISGs). This study aims to evaluate the impact of cisplatin on cGAS-STING pathway activity in ARID1A-deficient MB49 bladder cancer cell lines. Experiments were conducted using MB49 shARID1A and shScramble cells, both with and without cisplatin resistance. Knockdown validation was performed through qPCR and western blot analysis, while the resistant phenotype was confirmed using cytotoxicity assays. Following cisplatin treatment, the expression levels of cGAS-STING downstream target genes—including IFNB1, ISG15, CCL5, CXCL9, and CXCL10—were analyzed by qPCR. The results showed that cisplatin significantly upregulated the expression of these genes in ARID1A-deficient cells, indicating enhanced activation of the cGAS-STING pathway. These findings suggest that cisplatin not only exerts cytotoxic effects but also enhances antitumor immune responses through innate immune activation. The observed anomalies in cGAS-STING pathway gene expression in cisplatin-resistant MB49 cells highlight the need for further investigation to clarify the signaling mechanisms in cisplatin-resistant cancer cell lines.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | MB49, GEN ARID1A, CISPLATIN, cGAS-STING |
| Subjects: | Q Science > QH Biology Q Science > QH Biology > QH426 Genetics |
| Divisions: | Faculty of Science and Data Analytics (SCIENTICS) > Biology > 46101-(S2) Master Thesis |
| Depositing User: | Syakirah Shafwah Rahmadani |
| Date Deposited: | 04 Aug 2025 04:40 |
| Last Modified: | 04 Aug 2025 04:40 |
| URI: | http://repository.its.ac.id/id/eprint/125264 |
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