Abstract
Cisplatin is regularly used in the treatment of ovarian cancer. However, the drug only provides a modest survival advantage, primarily due to chemoresistance and the upregulation of antiapoptotic machineries in ovarian cancer cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in ovarian cancer cells may improve the therapeutic outcomes. Twist basic helix-loop-helix transcription factor 2 (Twist2) is a novel zinc finger transcription factor that has been indicated to be an important inducer of epithelial-mesenchymal transition, which has been shown to be involved in various phases of tumorigenicity and progression. However, whether Twist2 suppression increases the chemosensitivity of ovarian cancer cells to chemotherapeutic agents remains unclear. In the present study, Twist2 expression was found to differ between human ovarian cisplatin-sensitive cancer cell line, OV2008, and the resistant variant, C13K cells. Twist2 plasmids or RNA interference were then utilized to alter Twist2 expression in OV2008 or C13K cells, respectively, to further assess apoptosis, cell viability and cell growth, as well as a possible mechanism. The results of the present study indicated that Twist2 plays a crucial role in the chemoresistance of ovarian cancer. In addition, the downregulation of Twist2 expression may facilitate apoptosis and recover the sensitivity of chemoresistant ovarian cancer through the protein kinase B/glycogen synthase kinase-3β pathway. Therefore, Twist2 depletion may be a promising approach to ovarian cancer therapy.
Highlights
Ovarian cancer is the fifth most common cause of cancer‐related mortality in females and accounts for the highest tumor‐associated mortality of gynecological malignancies [1]
Chemoresistance increases in ovarian cancer due to high expression levels of Twist basic helix‐loop‐helix transcription factor 2 (Twist2)
OV2008 and C13K cells were treated with 10 μM cisplatin for 24, 48, 72 and 96 h expression was detected with quantitative polymerase chain reaction
Summary
Ovarian cancer is the fifth most common cause of cancer‐related mortality in females and accounts for the highest tumor‐associated mortality of gynecological malignancies [1]. Late diagnosis of ovarian cancer and ineffective chemotherapy has resulted in the number of mortalities from ovarian cancer exceeding that of any other cancer of the female reproductive system [2]. More than 70% of patients with ovarian cancer are diagnosed in the advanced stages (International Federation of Gynecology and Obstetrics stages III and IV), where the cancer has spread beyond the ovary and treatment becomes increasingly ineffective [3]. The preferred treatment of human ovarian cancer is cisplatin‐centered chemotherapy, which can markedly decrease the mortality rate and lengthen the survival time for patients. The mechanism responsible for cisplatin chemoresistance in ovarian cancer remains poorly understood [4]
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