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Open Access 26-07-2023 | Pancreatic Cancer | Original Article

Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma

Authors: Hidemi Nishi, Kunihito Gotoh, Yoshito Tomimaru, Shogo Kobayashi, Kazuki Sasaki, Yoshifumi Iwagami, Daisaku Yamada, Hirofumi Akita, Tadafumi Asaoka, Takehiro Noda, Hidenori Takahashi, Masahiro Tanemura, Yuichiro Doki, Hidetoshi Eguchi

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2023

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Abstract

Purpose

Although gemcitabine-based chemotherapy is most recommended for pancreatic ductal adenocarcinoma (PDAC), its effectiveness is limited because of drug resistance. Given thalidomide’s anti-tumor effects in solid tumors, we investigated the effect of avadomide, a novel thalidomide analog, on PDAC and explored its anti-tumor mechanisms.

Methods

PDAC cell lines, including gemcitabine-resistant (GR) clones derived from MiaPaCa2 cells, were used to evaluate the effects of avadomide. An annexin V assay, a cell cycle assay, and western blot analysis were performed to explain the mechanism of avadomide as an anti-tumor reagent. Moreover, we investigated the anti-tumor effect on tumor growth using a subcutaneous xenograft murine model.

Results

Avadomide showed anti-tumor effects in human PDAC cell lines. The proportion of apoptotic cells and G0/G1 phase cells after avadomide treatment increased, especially in the GR PDAC clones. Western blot analysis also showed the induction of the apoptotic pathway by inhibiting the NF-κB process and G1 phase cell cycle arrest. The xenograft murine model revealed that the proportion of viable cells in the avadomide-treated group was lower than that in the untreated group.

Conclusion

Our findings suggest that avadomide could be a novel therapeutic option to overcome gemcitabine resistance in patients with PDAC.
Appendix
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Metadata
Title
Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma
Authors
Hidemi Nishi
Kunihito Gotoh
Yoshito Tomimaru
Shogo Kobayashi
Kazuki Sasaki
Yoshifumi Iwagami
Daisaku Yamada
Hirofumi Akita
Tadafumi Asaoka
Takehiro Noda
Hidenori Takahashi
Masahiro Tanemura
Yuichiro Doki
Hidetoshi Eguchi
Publication date
26-07-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2023
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-023-04531-w

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