The platinum and taxane drugs as a neoadjuvant and adjuvant chemotherapy are the most used for treatment of ovarian cancer (OC). In later stages of ovarian cancer, targeted therapy with monoclonal antibodies may be included in the treatment regimen. Sodium-dependent phosphate transporter NaPi2b is a perspective target for the ovarian cancer treatment with monoclonal antibodies since the overexpression of NaPi2b was found in about 90% of the cases of OC. Currently NaPi2b-specific therapeutic monoclonal antibodies XMT-1536 (NCT03319628) and XMT-1592 (NCT04396340) are successfully undergoing clinical trials for the treatment of ovarian and lung cancers. Previously it was shown that NaPi2b protein abundance decreased in OC tumors of patients after neoadjuvant therapy mainly including carboplatin, thus, the subsequent use the therapy of monoclonal antibodies might be not effective. Currently it is unknown which drug of the ovarian cancer neoadjuvant chemotherapeutic regimen is responsible for the decrease of the Napi2b protein abundance. Thereby, the aim of the research was to evaluate the effect of carboplatin on the NaPi2b mRNA and protein level in the OVCAR-4 ovarian cancer cell line.
The NaPi2b mRNA and protein level before and after carboplatin treatment of OVCAR-4 cells was determined by real-time PCR and Western-blotting respectively. The Statistical analysis was performed in GraphPad Prism software.
Low abundance of NaPi2b protein was revealed in OVCAR-4 cells after the carboplatin treatment in IC25 and IC50 concentrations within 48 and 72 hours. At the same time NaPi2b mRNA level decreased after carboplatin treatment in IC25 and IC50 concentrations only within 72 hours. A weak correlation was observed between NaPi2b mRNA level and NaPi2b protein abundance in OVCAR-4 cells before and after the carboplatin treatment.
Thus, we revealed that carboplatin decreased the NaPi2b mRNA and protein abundance. The created model can be used to study the mechanisms underlying the regulation of NaPi2b gene expression. The NaPi2b level in ovarian cancer cells after neoadjuvant therapy may be a predictive marker for prescribing monoclonal antibodies therapy in patients with ovarian carcinoma.
Kazan Federal University.
This paper has been supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030).
All authors have declared no conflicts of interest.