Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin.

Abstract

Chemotherapy is widely used for the treatment of ovarian cancer. Since chemotherapy resistance is the major cause of poor prognosis in patients with ovarian cancer, it is important to identify new methods to improve the efficacy of chemotherapy. Minichromosome maintenance complex component 2 (MCM2), which serves an essential role in DNA replication, has been recently identified as a novel proliferation marker with prognostic implications in multiple types of cancer. However, the role of MCM2 in ovarian cancer and its underlying molecular mechanisms remain unclear. Therefore, in the present study, the biological effects of MCM2 were investigated, particularly with respect to DNA damage and repair. In the present study, short hairpin RNA was employed to knockdown MCM2 expression in the A2780 ovarian cancer cell line. The sensitivity of A2780 cells to carboplatin was assessed by cell colony formation assay. The present results suggested that MCM2 knockdown inhibited the proliferation of tumor cells, induced G0/G1 phase arrest and did not exhibit effects on cell apoptosis. However, MCM2 knockdown significantly decreased the colony formation of A2780 cells treated with carboplatin. Furthermore, knockdown of MCM2 together with carboplatin treatment or UV irradiation increased the protein expression level of γ‑H2A histone family member X and p53 compared with control cells. The present data suggested that the increased sensitivity to carboplatin may occur via the p53‑dependent apoptotic response. Additionally, the present results suggested that knockdown of MCM2 may have therapeutic applications in enhancing the efficacy of carboplatin in patients with ovarian cancer.

• Authors: Minjie Deng, Jiajun Sun, Suhong Xie, Hui Zhen, Yanchun Wang, Ailing Zhong, Hongqin Zhang, Renquan Lu, Lin Guo
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 20 Issue 3 Pg. 2258-2266 (Sep 2019) ISSN: 1791-3004 [Electronic] Greece
• PMID: 31322224 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• RNA, Small Interfering
• Carboplatin
• MCM2 protein, human
• Minichromosome Maintenance Complex Component 2

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carboplatin (pharmacology)
• Cell Line, Tumor
• DNA Damage (drug effects)
• Female
• Humans
• Minichromosome Maintenance Complex Component 2 (genetics)
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• RNA Interference
• RNA, Small Interfering (genetics)