Crizotinib, a MET inhibitor, prevents peritoneal dissemination in pancreatic cancer

International Journal of Oncology
Soichi TakiguchiHaruo Iguchi

Abstract

Peritoneal dissemination is a frequent occurrence in pancreatic cancer, which is associated with a poor prognosis. MET is associated with the progression of pancreatic cancer; therefore, we evaluated the effect of a MET inhibitor, crizotinib, on peritoneal dissemination of pancreatic cancer. Crizotinib inhibited the growth of 8 pancreatic cancer cell lines with the IC50 ranging from 1.4 to 4.3 µM. Invasion of the pancreatic cancer cell line Suit-2, was suppressed in vitro at a concentration of 1.0 µM, which is sufficient for the inhibition of MET phosphorylation. This effect on cell invasion was also recapitulated by the reduction of MET expression in Suit-2 with siRNA. Crizotinib also inhibited RhoA activation in addition to MET phosphorylation. We further evaluated the effect of crizotinib on peritoneal dissemination of pancreatic cancer in vivo. Crizotinib reduced tumor burden and ascites accumulation due to development of peritoneal dissemination after inoculation of Suit-2. Taken together, crizotinib may be a potent drug for treating peritoneal dissemination of pancreatic cancer by inhibiting cancer cell proliferation and invasion, at least in part through the suppression of HGF/MET signaling and RhoA activation.

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Citations

Aug 12, 2020·Cancer Metastasis Reviews·Leela Rani AvulaChristine Alewine
Mar 12, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Herbert J ZehMichael T Lotze
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Zhiwei ShaoAnwen Shao
Dec 5, 2020·International Journal of Molecular Sciences·Srinivasa P PothulaMinoti V Apte
Apr 20, 2021·Frontiers in Medicine·Cangang ZhangHaibo Liu
Aug 3, 2021·Frontiers in Oncology·Penelope EdwardsIan Chau

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