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Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma

Simón Serrano, Sonia LU ; Tavecchio, Michele LU ; Mallik, Josef LU ; Grönberg, Alvar ; Elmér, Eskil LU orcid ; Kifagi, Chamseddine LU ; Gallay, Philippe ; Hansson, Magnus Joakim LU orcid and Massoumi, Ramin LU (2022) In Cancers 14(19).
Abstract
Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl isomerase activity—have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related... (More)
Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl isomerase activity—have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
14
issue
19
article number
4553
publisher
MDPI AG
external identifiers
  • scopus:85139825510
  • pmid:36230472
ISSN
2072-6694
DOI
10.3390/cancers14194553
language
English
LU publication?
yes
id
f2653d0e-2f06-4a88-bd9d-bff98b84b1a4
date added to LUP
2022-09-27 15:47:48
date last changed
2024-01-28 17:35:56
@article{f2653d0e-2f06-4a88-bd9d-bff98b84b1a4,
  abstract     = {{Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl isomerase activity—have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment.}},
  author       = {{Simón Serrano, Sonia and Tavecchio, Michele and Mallik, Josef and Grönberg, Alvar and Elmér, Eskil and Kifagi, Chamseddine and Gallay, Philippe and Hansson, Magnus Joakim and Massoumi, Ramin}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  number       = {{19}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma}},
  url          = {{http://dx.doi.org/10.3390/cancers14194553}},
  doi          = {{10.3390/cancers14194553}},
  volume       = {{14}},
  year         = {{2022}},
}