Anti-Cancer Mechanism of Carboplatin and Paclitaxel in Ovarian Epithelial Cancer Cells

Background: The application of chemotherapy using the combination of platinum and taxane agents is now considered the standard treatment option for ovarian cancer. Notably, cells respond to DNA damage by promoting DNA repair; however, when repair is insufficient, cell death is induced. The abnormality of the nuclear pore complex (NPC) also leads to nuclear envelope destruction and disrupts transmembrane transport, leading to abnormal substance exchange. Therefore, this study aimed to analyze the mechanisms through which DNA damage induced by carboplatin and paclitaxel contributes to the treatment of ovarian epithelial cancer and to explore the role of DNA damage in mediating the anti-tumor effects of these compounds. Methods: Cell proliferation, cell cycle progression, and apoptosis were examined in four ovarian epithelial cancer cell lines following treatment with carboplatin, paclitaxel, or a combination of both compounds. A water-soluble tetrazolium-1 (WST-1) assay was employed to assess proliferation, flow cytometry was used for cell cycle analysis, and an immunofluorescence (IF) assay was utilized to detect apoptosis in the MES-OV (MOV), A2780, OVCAR-3, and OVCAR-5 cell lines. An IF assay was also used to evaluate nuclear structure and assess DNA damage. Results: Our study revealed that carboplatin and paclitaxel inhibited cell proliferation and induced cell cycle arrest, which was caused by DNA damage. In addition, paclitaxel induced an irreversible DNA damage, characterized by multimicronucleation, which is associated with NPC inhibition. Conclusions: Carboplatin and paclitaxel inhibit the proliferation of ovarian cancer cells, induce cell cycle arrest, and promote apoptosis by inducing DNA damage. This is associated with irreversible micronucleation and may be linked to NPC suppression, as well as the disruption of the microfilament and microtubule assembly. Moreover, studying the formation and anti-tumor mechanism of irreversible micronucleation has potential implications for enhancing the efficacy of cytotoxic chemotherapy in killing tumor cells.