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. 2022 Apr 14;22(1):411.
doi: 10.1186/s12885-022-09528-x.

Role of APOA1 in the resistance to platinum-based chemotherapy in squamous cervical cancer

Yue He  1 , Su-Bin Han  1 , Yang Liu  1 , Jing-Jing Zhang  1 , Yu-Mei Wu  2
Affiliations

Role of APOA1 in the resistance to platinum-based chemotherapy in squamous cervical cancer

Yue He et al. BMC Cancer. .

Abstract

Background: To investigate the mechanism by which apolipoprotein A1 (APOA1) enhances the resistance of cervical squamous carcinoma to platinum-based chemotherapy.

Methods: Two cervical squamous carcinoma cell lines (SiHa and Caski) overexpressing APOA1 were constructed, treated with carboplatin, and compared to normal control cells.

Results: In both SiHa and Caski cell lines, the clone-forming ability of CBP-treated cells was lower than that of untreated cells, and the change in the number of clones of overexpressing cells was lower than that of normal control cells (p < 0.05), indicating that APOA1 overexpression enhanced chemoresistance. A screen for APOA1 downstream proteins affecting platinum-based chemoresistance using Tandem Mass Tag revealed 64 differentially expressed proteins in SiHa cells, which were subjected to Gene Ontology (annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, subcellular localization, structural domain annotation and enrichment, clustering, and interaction network analyses. Sixty-four differentially expressed proteins matching cancer-relavent association terms were screened and parallel response monitoring identified 29 proteins as possibly involved in the mechanism of platinum-based chemoresistance.

Conclusions: Our analysis suggested that the mechanism may involve numerous regulatory pathways, including promoting tumor growth via the p38 MAPK signaling pathway through STAT1, promoting tumor progression via the PI3K signaling pathway through CD81 and C3, and promoting resistance to platinum-based chemotherapy resistance through TOP2A. The present study aimed to preliminarily explore the function and mechanism of APOA1 in platinum-based chemoresistance in cervical cancer, and the detailed mechanism needs to be further studied.

Keywords: Apolipoprotein A1; Cervical cancer; Chemotherapy resistance; Platinum,Proteomics.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Clone formation assay of APOA1-overexpressing SiHa and Caski cells
Fig. 2
Fig. 2
Clone formation histogram of APOA1-overexpressing SiHa and Caski cells. NC: SiHa or Caski cells with control lentivirus, OE: SiHa or Caski APOA1-overexpressing cells, NC + CBP: SiHa or Caski cells with control lentivirus treated with CBP for 48 h, OE + CBP: SiHa or Caski APOA1-overexpressing cells treated with CBP for 48 h
Fig. 3
Fig. 3
MTT assay to assess the effect of APOA1 overexpression on the proliferation of SiHa and Caski cells. NC: SiHa or Caski cells with control lentivirus, OE: SiHa or Caski APOA1-overexpressing cells, NC + CBP: SiHa or Caski cells with control lentivirus treated with CBP for 48 h, OE + CBP: SiHa or Caski APOA1-overexpressing cells treated with CBP for 48 h
Fig. 4
Fig. 4
TUNEL assay to detect the effect of APOA1 overexpression on apoptosis of SiHa/Caski cells with and without CBP. NC: SiHa or Caski cells with control lentivirus, OE: SiHa or Caski APOA1-overexpressing cells, NC + CBP: SiHa or Caski cells with control lentivirus treated with CBP for 48 h, OE + CBP: SiHa or Caski APOA1-overexpressing cells treated with CBP for 48 h
Fig. 5
Fig. 5
GO enrichment analysis of the differentially expressed proteins in cells overexpressing APOA1 and normal control cells treated with carboplatin. (Tag:The ordinate represents the GO function name, and the abscissa represents the enrichment significance p-value.)
Fig. 6
Fig. 6
KEGG pathway enrichment analysis of the differentially expressed proteins in cells overexpressing APOA1 and normal control cells treated with carboplatin. (Tag:The ordinate represents the KEGG pathway name, and the abscissa represents the enrichment significance p-value)
Fig. 7
Fig. 7
Subcellular localization of the differentially expressed proteins in cells overexpressing APOA1 and normal control cells treated with carboplatin
Fig. 8
Fig. 8
Structural domain annotation and enrichment analysis in cells overexpressing APOA1 and normal control cells treated with carboplatin
See this image and copyright information in PMC

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