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Vpliv kanabinoidnih substanc na glioblastom z različno izraženimi receptorji CB1 in CB2
Žvar Baškovič, Barbara (Author), Lah Turnšek, Tamara (Mentor) More about this mentor... This link opens in a new window, Novak, Metka (Co-mentor)

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Abstract
Možganski tumor glioblastom (GB) je neozdravljiva bolezen z le kratkim preživetjem po diagnozi. Standardni načini zdravljenja so kirurška odstranitev, obsevanje in nekateri kemostatiki, kar pa bolnika zaščiti le pred zgodnjo ponovitvijo tumorja, ki je povprečno poldrugo leto. Ena od potencialnih novih terapij je uporaba oziroma so-uporaba različnih vrst kanabinoidov (npr. tetrahidrokanabinol, kanabidiol). Iz objavljenih študij je razvidno, da te substance spodbujajo apoptozo ter zavirajo angiogenezo in invazijo glioblastomskih celic. Namen tega dela je bil ugotoviti izražanje proteinov in genov kanabinoidnih receptorjev CB1 in CB2 v glioblastomskih celicah in tkivih. Nadalje smo doličili vpliv dveh vrst kanabinoidnih izvlečkov, ki vsebujeta večje količine bodisi tetrahidrokanabinola ali kanabidiola, na viabilnost celic GB ter matičnih celic GB ter primarnih kulturah celic bolnikov. Naši rezultati kažejo, da različne linije GB izražajo receptorje CB1 in CB2, oba se izražata tudi v normalnih astrocitih. V kulturah GMC linij smo izražanje receptorjev potrdili še z imunofluorescenco in ugotovili visoke vsebnosti CB1 in CB2 proteinov. Izražanje gena za CB1, CNR1, smo zaznali tako v vzorcih tkiv GB in v celicah GB. Potrdili smo opazno zmanjšanje viabilnosti celic GB ob dodatku kanabinoidnih smol. GB je heterogen tumor in možno je, da se tumorji razlikujejo tudi v vsebnosti kanabinoidnih receptorjev. V kolikor ti sovpadajo z odzivnostjo bolnikovih celic na odgovarjajoče kanabinoide, bi lahko bolj informirano pristopili k personalizirani uporabi v kliničnem zdravljenju, ki bi bila prirejena izražanju kanabinoidnih receptorjev.

Language:Slovenian
Keywords:možganski tumor, glioblastom, kanabinoidi, THC, CBD, kanabinoidni receptorji, CB1, CB2
Work type:Master's thesis/paper (mb22)
Tipology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Year:2019
Publisher:[B. Žvar Baškovič]
UDC:616.714.1-006:615.277.3:582.630.1
COBISS.SI-ID:5106040 Link is opened in a new window
Views:200
Downloads:87
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Secondary language

Language:English
Title:Influence of cannabinoids on glioblastoma with differentially expressed receptors CB1 and CB2
Abstract:
The brain tumor glioblastoma (GB) is an incurable disease and only allows short lifespan after diagnosis. Standard therapeutic approaches that include surgical tumor removal, irradiation and chemotherapy are not very efficiently prolonguing the time of GB recurrence. One of the potential new options is the use of different types of cannabinoids (such as tetrahydrocannabinol and cannabidiol). From published studies it is evident that these substances induce apoptosis and inhibit angiogenesis and invasion of GB. The purpose of this work was to determine the expression of proteins and genes of cannabinoid receptors CB1 and CB2 in GB cells and tissues. Furthermore, we determined the influence of two types of cannabinoid extracts, that contain relatively higher amounts of either tetrahydrocannabinol or cannabidiol, on the viability of established GB cells, GB stem cells and the primary cultures of patient-derived cells. Our results show that different GB cell lines express both CB1 and CB2 receptor proteins, which are also expressed in normal astrocites. In GB stem cell lines, the expression of receptors was also determined by immunofluorescence, and we found significantly high contents of CB1 and CB2. The expression of the GB genes, i.e. CNR1 gene, was detected both in GB cells and in GB tissues. We have confirmed a decrease in the viability of GB cells when Cannabinoid resins were added. GB is a heterogenous tumor and it is possible that they as well differ in the content of cannabinoid receptors. If the levels of receptors coincide with the responsiveness of the patient's cells to the corresponding cannabinoids, a more informed personalized approach of their clinical use could be applied, related to the expression of their receptors.

Keywords:brain tumor, glioblastoma, cannabinoids, THC, CBD, cannabinoid receptors, CB1, CB2

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