Downregulation of high mobility group protein box-1 resensitizes ovarian cancer cells to carboplatin.

Abstract

Ovarian cancer, one of the most common types of cancer, has the highest mortality among all gynecological malignancies. The development of acquired drug resistance is the leading cause of chemotherapy failure. To study the mechanism underlying drug resistance in ovarian cancer, a drug-resistant ovarian cancer SKOV3 cell line was developed using the chemotherapeutic agent carboplatin (SKOV3-Carb) in the present study. It has been reported that high-mobility group protein box-1 (HMGB1) is associated with the chemoresistance of tumor cells. Therefore, the probable involvement of HMGB1 in the development of carboplatin resistance in ovarian cancer SKOV3 cells was investigated. HMGB1 has been reported to be overexpressed in carboplatin-resistant SKOV3-Carb cells compared with control SKOV3 cells. Subsequently, the expression of HMGB1 was silenced by small interference RNA technology. Reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that mRNA and protein expression levels of HMGB1 were significantly inhibited in HMGB1-silenced cells. Cell proliferation and apoptosis analyses were performed to evaluate the effect of HMGB1 silencing on resistant ovarian cancer cells. An MTT assay revealed that the proliferation of HMGB1-silenced SKOV3 and SKOV3-Carb cells were decreased compared with the proliferation of non-silenced control cells. Additionally, HMGB1 protein expression levels in SKOV3 cells, but not in SKOV3-Carb cells, were decreased in response to carboplatin treatment. Annexin V-fluorescein isothiocyanate/propidium iodide staining demonstrated that HMGB1 silencing enhanced the effects of carboplatin in inducing the apoptosis of SKOV3-Carb cells relative to HMGB1 non-silenced control cells. The results of the present study suggested that HMGB1 may be involved in the development of carboplatin resistance in ovarian cancer SKOV3 cells and that HMGB1 silencing may induce the sensitization of carboplatin-resistant ovarian cancer cells to carboplatin. Therefore, HMGB1 may be considered as a potent therapeutic target for increasing the sensitivity of ovarian cancer cells to carboplatin in order to improve the treatment and prognosis of ovarian cancer.