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Investigational New Drugs
Erschienen in:

28.06.2024 | Research

Auger emitter in combination with Olaparib suppresses tumor growth via promoting antitumor immune responses in pancreatic cancer

verfasst von: Yanqi Zhong, Heng Zhang, Peng Wang, Jing Zhao, Yuxi Ge, Zongqiong Sun, Zi Wang, Jie Li, Shudong Hu

Erschienen in: Investigational New Drugs | Ausgabe 4/2024

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Abstract

The present study aimed to clarify the hypothesis that auger emitter 125I particles in combination with PARP inhibitor Olaparib could inhibit pancreatic cancer progression by promoting antitumor immune response. Pancreatic cancer cell line (Panc02) and mice subcutaneously inoculated with Panc02 cells were employed for the in vitro and in vivo experiments, respectively, followed by 125I and Olaparib administrations. The apoptosis and CRT exposure of Panc02 cells were detected using flow cytometry assay. QRT-PCR, immunofluorescence, immunohistochemical analysis, and western blot were employed to examine mRNA and protein expression. Experimental results showed that 125I combined with Olaparib induced immunogenic cell death and affected antigen presentation in pancreatic cancer. 125I in combination with Olaparib influenced T cells and dendritic cells by up-regulating CD4, CD8, CD69, Caspase3, CD86, granzyme B, CD80, and type I interferon (IFN)-γ and down-regulating Ki67 in vivo. The combination also activated the cyclic GMP-AMP synthase stimulator of IFN genes (Sting) pathway in Panc02 cells. Moreover, Sting knockdown alleviated the effect of the combination of 125I and Olaparib on pancreatic cancer progression. In summary, 125I in combination with Olaparib inhibited pancreatic cancer progression through promoting antitumor immune responses, which may provide a potential treatment for pancreatic cancer.
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Metadaten
Titel
Auger emitter in combination with Olaparib suppresses tumor growth via promoting antitumor immune responses in pancreatic cancer
verfasst von
Yanqi Zhong
Heng Zhang
Peng Wang
Jing Zhao
Yuxi Ge
Zongqiong Sun
Zi Wang
Jie Li
Shudong Hu
Publikationsdatum
28.06.2024
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 4/2024
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-024-01454-y

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