1. Academic Validation
  2. Anti-tumor effect of avadomide in gemcitabine-resistant pancreatic ductal adenocarcinoma

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

  • Cancer Chemother Pharmacol. 2023 Jul 26. doi: 10.1007/s00280-023-04531-w.
Hidemi Nishi 1 Kunihito Gotoh 1 Yoshito Tomimaru 1 Shogo Kobayashi 2 Kazuki Sasaki 1 Yoshifumi Iwagami 1 Daisaku Yamada 1 Hirofumi Akita 1 Tadafumi Asaoka 1 Takehiro Noda 1 Hidenori Takahashi 1 Masahiro Tanemura 1 Yuichiro Doki 1 Hidetoshi Eguchi 1
Affiliations

Affiliations

  • 1 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 2 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan. skobayashi@gesurg.med.osaka-u.ac.jp.
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.

Keywords

Avadomide; Gemcitabine-resistant; Pancreatic cancer; Xenograft murine model.

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