Efek Eksosom Human Wharton's Jelly Mesenchymal Stem Cells Terhadap Progresivitas Kanker : Regulasi Cell Cycle, Proliferasi, dan Kemampuan Migrasi

Fatiha Citra Effendi, drh. Retno Murwanti, MP., PhD

2025 | Skripsi | FARMASI

Kanker payudara Luminal A menyumbang angka kekambuhan terbanyak dalam jangka kurang dari 5 tahun, dengan prevalensi mencapai 70?ri total kasus. Eksosom Human Wharton's Jelly (EHWJ) merupakan vesikel ekstraseluler dari jaringan tali pusat yang mengandung miRNA guna menghambat pertumbuhan sel kanker. Dengan demikian, eksosom berpotensi sebagai terapi penghambat progresivitas kanker. Penelitian ini bertujuan mengeksplorasi efek EHWJ dalam menghambat progresivitas kanker, terkhusus pada regulasi cell cycle, proliferasi, dan kemampuan migrasi. Jenis sel yang digunakan adalah MCF-7 cell line sebagai model subtipe Luminal A. Metode yang digunakan mencakup uji antiproliferasi dengan MTT assay, uji antimigrasi sel dengan scratch wound healing assay, analisis cell cycle dengan flow cytometry, serta evaluasi ekspresi gen TGF-?, Smad2, p21, dan SNAIL dengan qRT-PCR. Analisis statistik data dilakukan dengan Two-way dan One-way ANOVA menggunakan software SPSS (p <0>

Konsentrasi rendah EHWJ menyebabkan penurunan %viabilitas sel secara signifikan sebagai representasi efek penghambatan proliferasi (p <0 xss=removed>p <0 xss=removed>p <0 xss=removed>cell cycle, diketahui terdapat arrest pada fase G0/G1 akibat perlakuan EHWJ 2,1x104 partikel/mL yang diduga sebagai respon senescence, sedangkan perlakuan EHWJ 4,2x104 partikel/mL tidak terjadi perubahan progresi siklus (p >0,05) yang diduga sebagai reversible arrest. Hasil qRT-PCR menunjukkan konsentrasi rendah EHWJ (2,1x104 dan 4,2x104) mengalterasi TGF-? pathway sebagai tumor supressor melalui upregulasi gen TGF-?, Smad2, dan p21. Di samping itu, diketahui tidak terjadi perubahan ekspresi gen SNAIL pada EHWJ 4,2x104 partikel/mL (p >0,05), sedangkan pada EHWJ 2,1x104 partikel/mL mengalami downregulasi (p <0 xss=removed>cell cycle, serta alterasi gen TGF-? pathway sebagai tumor supressor.

The Luminal A subtype exhibited high recurrence rate, up to 70% of cases within five years. Exosomes isolated from Human Wharton’s Jelly (EHWJ) are extracellular vesicles derived from umbilical cord tissue containing microRNAs that showed cancer growth inhibition capability. Thus, EHWJ became a promising therapeutic candidate. This study examined the role of EHWJ on breast cancer progression in MCF-7 cell-line model of Luminal A subtype, focused on cell cycle regulation, proliferation, and migration. The methods comprised MTT assay to assess cell viability, scratch wound healing assay to evaluate migratory capacity, flow cytometry to analyze cell cycles, and qRT-PCR to measure TGF-?, Smad2, p21, and SNAIL gene expression. Statistical analyses were performed using two-way and one-way ANOVA with SPSS software (p-values <0>

Results demonstrated that EHWJ low concentrations significantly reduced cell viability, reflecting an antiproliferative effect. Proliferation was further suppressed at 72 hours of incubation treatment at both low and medium concentrations. Scratch assays revealed effective migratory inhibition at EHWJ low concentrations, whereas high concentrations induced morphological changes associated with epithelial-to-mesenchymal transition (EMT). Cell cycle analysis indicated G0/G1-arrest at the concentration of 2.1×10? particles/mL possibly underwent senescence. In contrast, treatment of EHWJ 4.2×10? particles/mL did not significantly affect cell cycle progression, possibly modulating cytostasis. Additionally, qRT-PCR results showed that EHWJ low concentration upregulated tumor-suppressor genes of TGF-? pathway, including TGF-?, Smad2, and p21. Parallelly, there was no significant change in SNAIL expression at EHWJ 4.2×10⁴ particles/mL, whereas a significant downregulation was observed at EHWJ 2.1×10⁴ particles/mL. In conclusion, these findings suggest that EHWJ effectively suppressed cancer progression by inhibiting proliferation and migration, regulating the cell cycle, and altering TGF-? tumor suppressor pathway.

Kata Kunci : Wharton's Jelly-derived exosomes, cancer, cell cycle, proliferation, migration, TGF-? pathway.