Matches in SemOpenAlex for { <https://semopenalex.org/work/W3007667695> ?p ?o ?g. }
- W3007667695 abstract "Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant solid tumours and its treatment has not been efficiently improved during the last decade. The overall 5-year survival rate of pancreatic cancer is 9%, which is expected to become the second major cause of cancer-related mortality by 2030. Chemotherapy has been used as the main treatment of choice in the majority of patients bearing either locally advanced or metastatic tumours. Gemcitabine alone or gemcitabine-based combination chemotherapy is commonly used worldwide for the treatment of pancreatic cancer. The poor treatment response to chemotherapy might be related to a dense stroma that is associated with these cancers. However, more effective treatment techniques and novel targets are urgently needed to improve the treatment response. Plant-derived cannabinoids have been used for medical purposes for over a thousand years. The main active cannabinoid components are tetrahydrocannabinol (THC) and cannabidiol (CBD) that are obtained from Cannabis sativa and Cannabis indica. THC exerts its effects via a receptor dependent mechanism, while CBD can act through a receptor and receptor independent mechanisms. CBD can modulate the adverse effects of THC such as its psychoactive effects. To date, three cannabinoids receptors have been identified, CB1, CB2, and GPR55, which are located on the cell membrane and members of the G-protein coupled receptor (GPCR) family. Cannabinoid receptors play an important role in biological and pathological activities such as inflammation, oxidative stress, metabolism, fibrosis, appetite control, memory and emotion. The main aims of this study were to look at the expression of cannabinoid receptors in pancreatic cancer cell lines and pancreatic cancer specimens, detect the correlation of cannabinoid receptors expression with patient’s outcome, determine the effect of cannabinoids alone or in combination with chemotherapy on pancreatic cancer cells in vivo and in vitro.Methods: Western blot assay, SRB-assay, immunohistochemistry staining, wound healing assay and an animal model were the main methods used in this study.Results: The expression of CB1 and CB2 receptors were shown in all the human and murine pancreatic cancer cell lines, stellate cells, and the gemcitabine resistant cell lines. The significant correlation between high expression of GPR55 and worsened PDAC patients’ outcome were demonstrated. In addition, the positive surgical margin and moderate to dense stromal status are associated with a poorer and prolonged survival in patients, respectively. Both CBD and THC dose-dependently inhibited cell proliferation of pancreatic cancer cells, although CBD was more effective than THC. All the different combination ratios of CBD to THC showed significant effects on the inhibition of cancer cell proliferation compared with a single treatment of drugs, although a 1:1 ratio of THC to CBD demonstrated the maximal inhibitory effect on cell proliferation and migration. Synergistic inhibition was observed for combined THC and CBD treatments, and when THC/CBD was combined. with gemcitabine (combination index < 1; using the Chou-Talalay method). In this study, cannabis oil, which contained a 1:1 ratio of CBD to THC and other cannabinoid components has been used for in vitro and in vivo experiments. The effects of this oil on pancreatic cancer cell proliferation and migration was less than either the pure CBD or THC alone. Moreover, cannabis oil alone or in combination with gemcitabine did not significantly inhibit tumour growth in a xenograft model. Bioavailability and absorption patterns of this oil are unknown and further studies are required.Conclusion: Cannabinoid receptors are highly expressed in pancreatic cancer cell lines. The high intensity of GPR55 was correlated with poor patients’ outcome. The 1:1 ratio of THC to CBD provided a significant inhibitory effect on pancreatic cancer proliferation and migration. Combination of cannabinoids with gemcitabine had a synergistic effect on pancreatic cancer inhibition in in vitro study. The cannabis oil used in our in vitro study showed a lesser effect on blocking proliferation and migration of cancer cells than purified THC and CBD. We could not determine the clinically significant effect on pancreatic cancer in our in vivo study using cannabis oil. No absorption characteristics of studied cannabis oil have been reported, therefore more in vivo bioavailability studies are required for the future work." @default.
- W3007667695 created "2020-03-06" @default.
- W3007667695 creator A5047671035 @default.
- W3007667695 date "2019-01-01" @default.
- W3007667695 modified "2023-09-27" @default.
- W3007667695 title "The effects of cannabinoid derivatives on pancreatic cancer" @default.
- W3007667695 cites W1032058218 @default.
- W3007667695 cites W1434138403 @default.
- W3007667695 cites W1485494169 @default.
- W3007667695 cites W1497915798 @default.
- W3007667695 cites W1537897316 @default.
- W3007667695 cites W1606521211 @default.
- W3007667695 cites W1636749516 @default.
- W3007667695 cites W1821794896 @default.
- W3007667695 cites W1887249759 @default.
- W3007667695 cites W1940834207 @default.
- W3007667695 cites W1964440995 @default.
- W3007667695 cites W1965087543 @default.
- W3007667695 cites W1966328410 @default.
- W3007667695 cites W1966551238 @default.
- W3007667695 cites W1967319651 @default.
- W3007667695 cites W1967942903 @default.
- W3007667695 cites W1968812902 @default.
- W3007667695 cites W1974642601 @default.
- W3007667695 cites W1975005333 @default.
- W3007667695 cites W1979368453 @default.
- W3007667695 cites W1981232081 @default.
- W3007667695 cites W1982003314 @default.
- W3007667695 cites W1984311964 @default.
- W3007667695 cites W1986360066 @default.
- W3007667695 cites W1986740576 @default.
- W3007667695 cites W1989732890 @default.
- W3007667695 cites W1990006357 @default.
- W3007667695 cites W1990694709 @default.
- W3007667695 cites W1991001962 @default.
- W3007667695 cites W1991212770 @default.
- W3007667695 cites W1993039760 @default.
- W3007667695 cites W1994187857 @default.
- W3007667695 cites W1995352070 @default.
- W3007667695 cites W1996177366 @default.
- W3007667695 cites W1998141662 @default.
- W3007667695 cites W2001036106 @default.
- W3007667695 cites W2002535987 @default.
- W3007667695 cites W2006627462 @default.
- W3007667695 cites W2007868976 @default.
- W3007667695 cites W2007952664 @default.
- W3007667695 cites W2008225047 @default.
- W3007667695 cites W2008357099 @default.
- W3007667695 cites W2013093033 @default.
- W3007667695 cites W2013655484 @default.
- W3007667695 cites W2015601936 @default.
- W3007667695 cites W2015614945 @default.
- W3007667695 cites W2015789312 @default.
- W3007667695 cites W2016371428 @default.
- W3007667695 cites W2017062859 @default.
- W3007667695 cites W2019927938 @default.
- W3007667695 cites W2020827621 @default.
- W3007667695 cites W2022334439 @default.
- W3007667695 cites W2024335876 @default.
- W3007667695 cites W2025793972 @default.
- W3007667695 cites W2027518631 @default.
- W3007667695 cites W2034306073 @default.
- W3007667695 cites W2036228294 @default.
- W3007667695 cites W2037232827 @default.
- W3007667695 cites W2038809664 @default.
- W3007667695 cites W2039716354 @default.
- W3007667695 cites W2040032122 @default.
- W3007667695 cites W2043687423 @default.
- W3007667695 cites W2044376607 @default.
- W3007667695 cites W2045162664 @default.
- W3007667695 cites W2046870314 @default.
- W3007667695 cites W2048461547 @default.
- W3007667695 cites W2049370911 @default.
- W3007667695 cites W2049413898 @default.
- W3007667695 cites W2050601193 @default.
- W3007667695 cites W2055037794 @default.
- W3007667695 cites W2056188558 @default.
- W3007667695 cites W2057739367 @default.
- W3007667695 cites W2059960512 @default.
- W3007667695 cites W2060180499 @default.
- W3007667695 cites W2060231477 @default.
- W3007667695 cites W2062300012 @default.
- W3007667695 cites W2064919180 @default.
- W3007667695 cites W2067927629 @default.
- W3007667695 cites W2070810477 @default.
- W3007667695 cites W2071824065 @default.
- W3007667695 cites W2072225171 @default.
- W3007667695 cites W2075560989 @default.
- W3007667695 cites W2075894678 @default.
- W3007667695 cites W2080537530 @default.
- W3007667695 cites W2080714050 @default.
- W3007667695 cites W2081040408 @default.
- W3007667695 cites W2082082322 @default.
- W3007667695 cites W2083438158 @default.
- W3007667695 cites W2083859343 @default.
- W3007667695 cites W2089039955 @default.
- W3007667695 cites W2090772524 @default.
- W3007667695 cites W2091808474 @default.
- W3007667695 cites W2093005174 @default.
- W3007667695 cites W2095368989 @default.