KRT17 enhances carboplatin resistance in ovarian cancer through the AKT/mTOR pathway
1Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, Jiangsu, China
DOI: 10.22514/ejgo.2022.032 Vol.43,Issue 4,August 2022 pp.49-57
Submitted: 13 May 2022 Accepted: 30 June 2022
Published: 15 August 2022
*Corresponding Author(s): Jie Zhou E-mail: email@example.com
Ovarian cancer has gradually evolved into a killer of women’s health. Keratin 17 (KRT17) belongs to keratin family. The role of KRT17 in ovarian cancer is not yet clear. Carboplatin-resistant cell lines of ovarian cancer were established, and the effect of carboplatin on the cell viability of SKOV3-CBP, A2780-CBP (carboplatin-resistant cell lines) and SKOV3, A2780 cells were investigated by MTT assay; the expression of KRT17 was predicted and verified by Gene Expression Profiling Interactive Analysis (GEPIA) and western blot (WB) to compare ovarian cancer and normal tissues; KRT17 was successfully knocked down in carboplatin-resistant cell lines, the effect of carboplatin on the cell viability of carboplatin-resistant cell lines and non-drug-resistant cell lines was studied by MTT assay, combined with colony formation assay to study the effect of knockdown of KRT17 on cell clonality; flow cytometry and WB to study the effect of knockdown of KRT17 on cell cycle and apoptosis, and targeted signaling pathway. The results showed that as for the expression of KRT17, compared to normal tissues, ovarian cancer was higher than that; SKOV3-CBP and A2780-CBP were not highly sensitive to drugs and had strong drug resistance. After knocking down KRT17, the drug resistance decreased, the cell cycle was arrested in G0/G1, the protein expression levels of Cyclin D1 and cyclin dependent kinase 4 (CDK4) decreased, the apoptosis level increased and the protein expression level increased; KRT17 mainly plays a regulatory role by targeting AKT/mammalian (or mechanistic) target of rapamycin (AKT/mTOR). This study found that KRT17 could increase the carboplatin resistance of ovarian cancer cells by regulating the AKT/mTOR pathway, promoting the cycle process of ovarian cancer cells, and inhibit apoptosis.
Ovarian cancer; AKT/mTOR; Carboplatin; Drug resistance
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