Scientific Reports (Mar 2024)

Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model

  • Trung Quang Le,
  • Nuntana Meesiripan,
  • Suleeporn Sanggrajang,
  • Nuntakan Suwanpidokkul,
  • Piyaporn Prayakprom,
  • Chatchada Bodhibukkana,
  • Vipada Khaowroongrueng,
  • Kankanit Suriyachan,
  • Somchai Thanasitthichai,
  • Attasit Srisubat,
  • Pattamaporn Surawongsin,
  • Anudep Rungsipipat,
  • Siriwan Sakarin,
  • Kasem Rattanapinyopituk

DOI
https://doi.org/10.1038/s41598-024-55307-y
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 16

Abstract

Read online

Abstract Human pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal tumor of the exocrine pancreas. Cannabinoids extracted from the hemp plant Cannabis sativa have been suggested as a potential therapeutic agent in several human tumors. However, the anti–tumor effect of cannabinoids on human PDAC is not entirely clarified. In this study, the anti–proliferative and apoptotic effect of cannabinoid solution (THC:CBD at 1:6) at a dose of 1, 5, and 10 mg/kg body weight compared to the negative control (sesame oil) and positive control (5-fluorouracil) was investigated in human PDAC xenograft nude mice model. The findings showed that cannabinoids significantly decreased the mitotic cells and mitotic/apoptotic ratio, meanwhile dramatically increased the apoptotic cells. Parallelly, cannabinoids significantly downregulated Ki-67 and PCNA expression levels. Interestingly, cannabinoids upregulated BAX, BAX/BCL-2 ratio, and Caspase-3, meanwhile, downregulated BCL-2 expression level and could not change Caspase-8 expression level. These findings suggest that cannabinoid solution (THC:CBD at 1:6) could inhibit proliferation and induce apoptosis in human PDAC xenograft models. Cannabinoids, including THC:CBD, should be further studied for use as the potent PDCA therapeutic agent in humans.

Keywords