Abstract
Simple SummaryPancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. The advantages of using cannabinoids have been evaluated in several human cancers. Regarding PC, activation of cannabinoid receptors was found to induce PC cell apoptosis without affecting the normal pancreas cells. Herein, we evaluate the anticancer effect of cannabidiol (CBD) and O2/O3, alone or in combination, on two human pancreatic ductal adenocarcinoma (PDAC) cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.
Highlights
Pancreatic cancer (PC) is a lethal malignancy with a 5-year survival of approximately 5–9% [1,2].The most common and aggressive type, among pancreatic malignancies, is pancreatic ductal adenocarcinoma (PDAC), an infiltrating neoplasm with glandular differentiation, that is the fourth cause of cancer related death worldwide [2,3,4]
The gene and protein expressions of CB1, CB2, TRPV1, TRPV2, TRPV3, TRPV4, Transient Receptor Potential Ankyrin 1 (TRPA1), and TRPM8 were evaluated in PANC-1 and MiaPaCa-2 cancer cell lines by qRT/PCR and Western Blot analysis
Gene and protein expression showed that CB1 and CB2 receptors are expressed in both cell lines without any significant difference for the CB1 receptor, while the CB2 protein level is higher in the PANC-1 cell line
Summary
Pancreatic cancer (PC) is a lethal malignancy with a 5-year survival of approximately 5–9% [1,2].The most common and aggressive type, among pancreatic malignancies, is pancreatic ductal adenocarcinoma (PDAC), an infiltrating neoplasm with glandular differentiation, that is the fourth cause of cancer related death worldwide [2,3,4]. Surgical resection followed by adjuvant chemotherapy is the main therapeutic strategy for the 10–20% of patients with resectable PDAC stage, but is less effective in the rest of patients that show locally advanced, non-resectable stages or distant metastasis [9,10] For these non-resectable patients, systemic chemotherapy is employed as first-line treatment, with different drugs as gemcitabine (GEM), capecitabine, 5-fluorouracil in monotherapy or in combination with radiotherapy [11]. New potential therapies such as immunotherapy based on checkpoint inhibitors and targeted therapy are under evaluation but these treatments showed limited efficacy and were unsuccessful in improving patients’ survival, especially for metastastic pancreatic cancer [4,12,13]
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