Projekt per år
Sammanfattning
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are used in ovarian cancer treatment and have greatly improved the survival rates for homologous recombination repair (HRR)-deficient patients. However, their therapeutic efficacy is limited in HRR-proficient ovarian cancer. Thus, sensitizing HRR-proficient ovarian cancer cells to PARP inhibitors is important in clinical practice. Here, a nanodrug, olaparib-Ga, was designed using self-assembly of the PARP inhibitor olaparib into bovine serum albumin through gallic acid gallium(III) coordination via a convenient and green synthetic method. Compared with olaparib, olaparib-Ga featured an ultrasmall size of 7 nm and led to increased suppression of cell viability, induction of DNA damage, and enhanced cell apoptosis in the SKOV3 and OVCAR3 HRR-proficient ovarian cancer cells in vitro. Further experiments indicated that the olaparib-Ga nanodrug could suppress RRM2 expression, activate the Fe 2+/ROS/MAPK pathway and HMOX1 signaling, inhibit the PI3K/AKT signaling pathway, and enhance the expression of cleaved-caspase 3 and BAX protein. This, in turn, led to increased cell apoptosis in HRR-proficient ovarian cancer cells. Moreover, olaparib-Ga effectively restrained SKOV3 and OVCAR3 tumor growth and exhibited negligible toxicity in vivo. In conclusion, we propose that olaparib-Ga can act as a promising nanodrug for the treatment of HRR-proficient ovarian cancer.
Originalspråk | Engelska |
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Sidor (från-till) | 12786-12800 |
Antal sidor | 15 |
Tidskrift | ACS Nano |
Volym | 16 |
Nummer | 8 |
DOI | |
Status | Publicerad - 23 aug. 2022 |
MoE-publikationstyp | A1 Tidskriftsartikel-refererad |
Fingeravtryck
Fördjupa i forskningsämnen för ”Breaking the Iron Homeostasis: A “Trojan Horse” Self-Assembled Nanodrug Sensitizes Homologous Recombination Proficient Ovarian Cancer Cells to PARP Inhibition”. Tillsammans bildar de ett unikt fingeravtryck.Utrustning
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Åbo Akademi Functional Printing Center
Toivakka, M. (PI), Rosenholm, J. (PI), Anttu, N. (PI), Bobacka, J. (PI), Huynh, T. P. (PI), Peltonen, J. (PI), Wang, X. (PI), Wilen, C.-E. (PI), Xu, C. (PI), Zhang, H. (PI) & Österbacka, R. (PI)
Fakulteten för naturvetenskaper och teknikUtrustning/facilitet: Facilitet
Projekt
- 2 Slutfört
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FCFH: Finland-China Network in Food and Health Sciences
Rosenholm, J. (Ansvarig forskare), Xu, C. (Ansvarig forskare) & Zhang, H. (Ansvarig forskare)
Undervisnings och kulturministeriet i Finland (UKM)
01/01/21 → 31/12/24
Projekt: Ministerier / Statliga myndigheter och verk
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Targeted delivery of CRISPR/Cas9 for advanced liver cancer therapy through c-Myc knockout
Zhang, H. (Ansvarig forskare)
01/09/19 → 31/08/24
Projekt: Finlands Akademi/Övriga Forskningsråd