Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells
The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro-apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt-Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear translocation. DNA-PKcs inhibition, knockdown or mutation facilitated TIC10-induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis. Reversely, exogenous DNA-PKcs over-expression inhibited above actions by TIC10. In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth in nude mice, which was further potentiated with Nu7026 co-administration. Thus, TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Oncotarget - 8(2017), 17 vom: 25. Apr., Seite 28385-28394 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cheng, Long [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.03.2018 Date Revised 09.12.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.18632/oncotarget.16073 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells |
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| 520 | |a The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro-apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt-Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear translocation. DNA-PKcs inhibition, knockdown or mutation facilitated TIC10-induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis. Reversely, exogenous DNA-PKcs over-expression inhibited above actions by TIC10. In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth in nude mice, which was further potentiated with Nu7026 co-administration. Thus, TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs inhibitors | ||
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| 700 | 1 | |a Lu, Pei-Hua |e verfasserin |4 aut | |
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| 700 | 1 | |a Gu, Xin-Shi |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Min-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Xu-Ming |e verfasserin |4 aut | |
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