Experimental cell research · 2026
Overexpression of scavenger receptor class B member 2 leads to different response of ovarian adenocarcinoma cells to chemotherapy.
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Harvanik Pavol, Solárová Zuzana, Danková Kristína, Bober Peter, Majerová Petra, Michalková Radka, Bhide Mangesh, Solár Peter
Аннотация
AIMS: Scavenger Receptor Class B Member 2 (SCARB2) is an integral lysosomal membrane protein essential for lysosomal integrity and autophagy regulation. The aim of this study was to investigate the functional impact of SCARB2 overexpression on chemotherapy response, reactive oxygen species (ROS) production and proteomic composition of human ovarian adenocarcinoma cells A2780.
METHODS: To induce SCARB2 overexpression, A2780 cells were transfected using a PiggyBac vector system. Two clones with the highest SCARB2 expression (L and V) were selected for further analyses. Differences in chemosensitivity were assessed using the MTS assay. Proteomic analysis was used to identify differentially expressed proteins and enriched pathways. We also performed flow cytometry to investigate changes in ROS production and lysosomal activity. Lysosomal distribution was assessed using LAMP1 immunofluorescence staining followed by confocal microscopy, and total cholesterol levels were determined using an enzymatic colorimetric assay.
RESULTS: Both clones showed increased sensitivity to cisplatin compared to the control group. In contrast, clone V showed resistance to doxorubicin and no significant differences were observed for gemcitabine, except for a transient sensitizing effect when low concentrations used. Elevated ROS levels were detected in untreated clones, and after doxorubicin exposition. Proteomic analysis showed significant changes in lysosome-associated proteins, with consistent enrichment of the lysosomal pathway across all experimental comparisons. Immunofluorescence analysis of LAMP1 and LysoTracker staining demonstrated altered lysosomal distribution and activity in SCARB2-overexpressing clones. In addition, both SCARB2-overexpressing clones exhibited significantly reduced total cholesterol levels compared with control cells.
CONCLUSIONS: This study broadens our understanding of SCARB2 in ovarian cancer. SCARB2 overexpression induces extensive lysosomal reprogramming in A2780 ovarian cancer cells and modulates chemotherapy response.
METHODS: To induce SCARB2 overexpression, A2780 cells were transfected using a PiggyBac vector system. Two clones with the highest SCARB2 expression (L and V) were selected for further analyses. Differences in chemosensitivity were assessed using the MTS assay. Proteomic analysis was used to identify differentially expressed proteins and enriched pathways. We also performed flow cytometry to investigate changes in ROS production and lysosomal activity. Lysosomal distribution was assessed using LAMP1 immunofluorescence staining followed by confocal microscopy, and total cholesterol levels were determined using an enzymatic colorimetric assay.
RESULTS: Both clones showed increased sensitivity to cisplatin compared to the control group. In contrast, clone V showed resistance to doxorubicin and no significant differences were observed for gemcitabine, except for a transient sensitizing effect when low concentrations used. Elevated ROS levels were detected in untreated clones, and after doxorubicin exposition. Proteomic analysis showed significant changes in lysosome-associated proteins, with consistent enrichment of the lysosomal pathway across all experimental comparisons. Immunofluorescence analysis of LAMP1 and LysoTracker staining demonstrated altered lysosomal distribution and activity in SCARB2-overexpressing clones. In addition, both SCARB2-overexpressing clones exhibited significantly reduced total cholesterol levels compared with control cells.
CONCLUSIONS: This study broadens our understanding of SCARB2 in ovarian cancer. SCARB2 overexpression induces extensive lysosomal reprogramming in A2780 ovarian cancer cells and modulates chemotherapy response.