53BP1 inhibits the migration and regulates the chemotherapy resistance of ovarian cancer cells

Abstract

Abstract. The major problems faced during the treatment of ovarian cancer are metastasis and the development of intrinsic or acquired drug resistance. The present study assessed whether tumor protein p53 binding protein 1 (53BP1) regulated migration and modulated chemotherapy resistance in SKOV3 cells and identified proteins associated with the molecular mechanisms underlying this coordinate regulation. SKOV3 cells were transfected using a 53BP1-expressing vector, which induced 53BP1 overexpression. The migration of the transfected cells was observed using a Transwell assay. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 were assayed using gelatin zymography. In addition, the effects of 53BP1 on the chemosensitivity of SKOV3 cells to cisplatin were evaluated using MTT and western blot assays. Compared with the control, the average number of migrating SKOV3/pLPC-53BP1 cells was decreased from 230±58 to 45±12 (P<0.05) and the protein expression of MMP-9 was significantly inhibited. However, the chemosensitivity of SKOV3/pLPC-53BP1 to cisplatin decreased significantly: Cisplatin half maximal inhibitory concentration (IC 50 ) for SKOV3/pLPC-53BP1=7.58±0.51 µg/ml; cisplatin IC 50 for control=2.98±0.27 µg/ml (P<0.01). Decreased chemosensitivity to cisplatin may be associated with increased expression of phosphorylated-protein kinase B and cyclin dependent kinase 2 and with decreased expression of p21 and the B cell lymphoma (Bcl)-2 associated X/Bcl-2 ratio. The results of the present study demonstrated that 53BP1 may inhibit migration but upregulate chemoresistance to cisplatin in SKOV3 cells.

MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2

“…23 Bcl-2 and Bax were confirmed to be related to the chemotherapy resistance in various tumors. 24 In our study, miR-23a inhibition was shown to suppress Bcl-2 expression but increase Bax expression, which was indicative of an accelerated OC cell apoptosis. Meanwhile, Oct-4, Nanog, and CD133 are known as stem cell markers and indicated as invasive and predictive markers in relation to a poor prognosis in oral squamous cell carcinoma (OSCC).…”

Downregulation of miR‑3934‑5p enhances A549 cell sensitivity to cisplatin by targeting TP53INP1

“…The resistance of tumor cells to DDP allows cells to evade the cytotoxic effects of DDP, overcoming apoptosis (23); however, the underlying molecular mechanisms of DDP resistance require further investigation (24,25). miRNAs have been reported to be regulators of DDP resistance in NSCLC.…”

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

“…This involves AKT translocating to the nucleus and becoming phosphorylated by DNA-PK, resulting in the inhibition of cisplatin-mediated apoptosis [ 52 ] ( Figure 2 ). A study has shown that the upregulation of 53BP1 in SKO3 ovarian carcinoma cells resulted in increased resistance to cisplatin [ 53 ] ( Figure 2 ). Finally, higher Ku70 expression is associated with a better response to cisplatin treatment and improved overall survival (OS) [ 54 ].…”