Peran TMEPAI (Transmembrane Prostate Andorgen-Induced) yang diinduksi TGF-pada resistensi sel kanker payudara triple-negative terhadap doksorubisin = The role of TGF-β-induced TMEPAI (transmembrane prostate androgen-induced) in the resistance of triple negative breast cancer cell to doxorubicin
Bantari Wisynu Kusuma Wardhani;
Rianto Setiabudy, promotor; Melva Louisa, co-promotor; Yukihide Watanabe, co-promotor; Rintis Noviyanti, examiner; Septelia
Inawati Wanand, examiner; Noorwaty Sutandyo, examiner; Vivian Soetikno, examiner
(Fakultas Kedokteran Universitas Indonesia, 2019)
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Latar belakang: Terapi farmakologi kanker payudara triple negative (KPTN)terbatas pada obat sitostatika seperti doksorubisin. Namun, resistensi doksorubisinsulit dihindari. Salah satu jalur pensinyalan yang penting pada resistensiKPTN terhadap doksorubisn adalah TGF-β. TMEPAI (transmembran prostatandrogen-induced protein), regulator negatif sekaligus gen target pada jalur TGF-β diduga merupakan salah satu kunci dalam resistensi KPTN terhadapdoksorubisin.Metode: Teknik CRISPR-Cas9 digunakan untuk menghilangkan TMEPAI padagalur sel KPTN, BT549. Sel diberi perlakuan TGF-β 2 ng / mL dan doksorubisinselama 24 jam. Pengukuran konsentrasi sitotoksik doksorubisin pada 50%populasi sel (CC50) dilakukan terhadap sel KPTN wildtype (WT) dan knock out(KO). Setelah itu, sel dipanen dan dihitung. Rantai Polimerase Waktu NyataReaction (RT-PCR) dan western blot (WB) digunakan untuk mengukur tingkatekspresi penande proliferasi, apoptosis, EMT, dan transporter. Selain itu, SMADyang terfosforilasi dan aktivitas PI3K / Akt juga belajar.Hasil: Galur sel yang tidak memiliki TMEPAI (KO) berhasil diperoleh dari selKPTN, BT549. Sel WT terbukti lebih resistan terhadap doksorubisindibandingkan sel KO yang ditunjukkan dengan peningkatan CC50 dan Ki-67.TMEPAI menurunkan efek apoptosis doksorubisin dengan memodulasi ekspresibcl-2 dan kaspase-3, namun tidak kaspase-9 dan bax. Efek TMEPAI mengurangidoksorubisin dengan menekan fosforilasi SMAD. Namun TMEPAI meningkatkanpenghambatan PI3K / Akt oleh doksorubisin. TMEPAI juga meningkatkan EMTdan transporter efluks yang diinduksi oleh doksorubisin.Kesimpulan: TMEPAI terhadap pertarungan dalam resistensi sel KPTNdoksorubisin melalui aktivasi jalur sinyal TGF-β non-canonical beserta proteindan gen targetnya.Background: Triple negative breast cancer (KPTN) pharmacological therapylimited to cytostatic drugs such as doxorubicin. However, doxorubicin resistancehard to avoid. One of the important signaling pathways of resistanceKPTN against doxorubisn is TGF-β. TMEPAI (transmembrane prostateandrogen-induced protein), a negative regulator as well as a target gene in the TGF-β is thought to be one of the keys in the resistance of KPTN todoxorubicin.Method: The CRISPR-Cas9 technique was used to remove TMEPAI onKPTN cell lines, BT549. Cells were treated with TGF-β 2 ng / mL and doxorubicinfor 24 hours. Measurement of the cytotoxic concentration of doxorubicin at 50%cell population (CC50) was carried out against wildtype KPTN (WT) cells and knockout(KO). After that, cells are harvested and counted. Real Time Polymerase ChainReaction (RT-PCR) and western blot (WB) were used to measure levelsexpression markers of proliferation, apoptosis, EMT, and transporters. Apart from that, SMADthe phosphorylated and PI3K / Akt activities also learn.Results: Cell lines that did not have TMEPAI (KO) were obtained from the cellsKPTN, BT549. WT cells have been shown to be more resistant to doxorubicincompared to cell knockout shown with increased CC50 and Ki-67.TMEPAI decreases the apoptotic effect of doxorubicin by modulating expressionbcl-2 and caspase-3, but not caspase-9 and bax. TMEPAI reducing effectsdoxorubicin by suppressing SMAD phosphorylation. However TMEPAI is improvingPI3K / Akt inhibition by doxorubicin. TMEPAI also increases EMTand doxorubicin-induced efflux transporters.Conclusion: TMEPAI against the fight against KPTN cell resistancedoxorubicin via activation of the non-canonical TGF-β signaling pathway along with proteinsand its target genes. |
D-Bantari Wisynu Kusuma Wardhani.pdf :: Unduh
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No. Panggil : | D-pdf |
Entri utama-Nama orang : | |
Entri tambahan-Nama orang : | |
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Subjek : | |
Penerbitan : | Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019 |
Program Studi : |
Bahasa : | ind |
Sumber Pengatalogan : | LibUI ind rda |
Tipe Konten : | text |
Tipe Media : | computer |
Tipe Carrier : | online resource |
Deskripsi Fisik : | xix, 78 pages : illustration ; 28 cm + appendix |
Naskah Ringkas : | |
Lembaga Pemilik : | Universitas Indonesia |
Lokasi : | Perpustakaan UI |
No. Panggil | No. Barkod | Ketersediaan |
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D-pdf | 07-21-905636713 | TERSEDIA |
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