ABC saimes gēnu ekspresija un vēža cilmes šūnu fenotipiskās izpausmes pret doksorubicīnu rezistentā MDA-MB-231 apakšpopulācijā
Date
2018
Authors
Samoviča, Marija
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Rezistence pret citotoksiskiem ķīmijterapijas savienojumiem ir nozīmīga problēma vēža ārstēšanā, kam raksturīga audzēja atjaunošanās un slimības progresēšana. Rezistenci pret ķīmijterapijas savienojumiem var veidot dažādi šūnu mehānismi, no kuriem visplašāk aprakstīta ATF saistošās kasetes (ABC) transportproteīnu pārekspresija. Rezistenci visbiežāk veicina pret ķīmijterapijas savienojumiem rezistentu apakšpopulāciju selekcija. Vēža cilmes šūnām (VCŠ) piemīt spēja izvairīties no ķīmijterapijas ietekmes un atjaunot audzēja šūnu populāciju. Darba mērķis bija noteikt ABC saimes gēnu ekspresiju un raksturot VCŠ raksturīgās pazīmes pret doksorubicīnu rezistentā trīskārši negatīva krūts vēža šūnu līnijas MDA-MB-231 apakšpopulācijā. Pēc punktveida apstrādes ar doksorubicīnu MDA-MB-231 šūnām gan uzreiz pēc apstrādes, gan nākamajā pasāžā tika konstatēta augstāka ABC transportproteīnu transkriptomiskā ekspresija lielākajai daļai no pārbaudītajiem ABC gēniem. Tika noteikta atsevišķu VCŠ marķieru gēnu pārekspresija un novērotas citas cilmšūnības izpausmes – spēja atjaunot populāciju un paaugstināta koloniju veidošanās spēja. Atjaunotajai šūnu populācijai, salīdzinot ar kontroles kultūru, bija paaugstināta rezistence pret doksorubicīnu.
Resistance to cytotoxic chemotherapy compounds is a significant problem in cancer treatment resulting in tumor regeneration and relapse. Chemoresistance can be mediated by various cell mechanisms, of which ATP binding casette (ABC) transporter overexpression is the most studied. Resistance often is mediated by selection of chemotherapy resistant subpopulations. Cancer stem cells (CSC) have the ability to avoid chemotherapy effects and to renew tumor cell population. The aim of this study was to determine ABC family gene expression and CSC characteristics in a doxorubicin resistant subpopulation of triple negative breast cancer cell line MDA-MB-231. After pulsed treatment with doxorubicin in MDA-MB-231 cells higher ABC transporter gene transcriptomic expression of most ABC family genes tested both after exposure and the following passage was determined. Overexpression of several CSC marker genes was found, and also other CSC characteristics were identified – ability to renew cell population and higher colony formation ability. The restored population had higher resistance to doxorubicin, compared to control culture.
Resistance to cytotoxic chemotherapy compounds is a significant problem in cancer treatment resulting in tumor regeneration and relapse. Chemoresistance can be mediated by various cell mechanisms, of which ATP binding casette (ABC) transporter overexpression is the most studied. Resistance often is mediated by selection of chemotherapy resistant subpopulations. Cancer stem cells (CSC) have the ability to avoid chemotherapy effects and to renew tumor cell population. The aim of this study was to determine ABC family gene expression and CSC characteristics in a doxorubicin resistant subpopulation of triple negative breast cancer cell line MDA-MB-231. After pulsed treatment with doxorubicin in MDA-MB-231 cells higher ABC transporter gene transcriptomic expression of most ABC family genes tested both after exposure and the following passage was determined. Overexpression of several CSC marker genes was found, and also other CSC characteristics were identified – ability to renew cell population and higher colony formation ability. The restored population had higher resistance to doxorubicin, compared to control culture.
Description
Keywords
Bioloģija , ķīmijterapijas rezistence , ABC saimes gēni , vēža cilmes šūnas , doksorubicīns , MDA-MB-231