OBJECTIVE To investigate the effects and mechanisms of schisandrin A in enhancing the chemosensitivity of paclitaxel-resistant ovarian cancer cells(A2780/TAX) to paclitaxel, providing novel insights into toxicity reduction and efficacy enhancement for ovarian cancer treatment.

METHODS A2780/TAX cells were cultured in vitro and divided into four groups: control group, paclitaxel group, schisandrin A group, and schisandrin A+paclitaxel group (combination). Cell viability was assessed via MTT assay. Apoptosis was detected by Annexin V-FITC/PI double staining using flow cytometry. Cell cycle distribution was analyzed by flow cytometry. The proliferative capacity was evaluated via colony formation assay and the migratory ability was tested by wound healing assay. The protein expression levels of AIF, XIAP, PARP, Cleaved PARP, Caspase 3, Cleaved Caspase 3, Caspase 7, and Cleaved Caspase 7 were measured via Western blotting assay. Transcriptome sequencing was performed to identify differentially expressed genes and cytoskeletal and nuclear morphology was visualized by immunofluorescence staining. The mRNA levels of CHEK1, CHEK2, CENPA, TTK, PRC1 and ANLN were detected by RT-qPCR.

RESULTS Schisandrin A combined with low-concentration paclitaxel significantly inhibited A2780/TAX cell viability and proliferation. The apoptosis rate in the combination group was markedly higher than in monotherapy groups. The results of Western blotting revealed that combination therapy downregulated AIF, XIAP, PARP, Caspase 3, and Caspase 7 expression while elevating Cleaved PARP, Cleaved Caspase 3, and Cleaved Caspase 7 levels. The combination group exhibited suppressed cell migration in wound healing assays. Transcriptome sequencing identified 1 515 upregulated and 1 582 downregulated DEGs between control and combination groups. GO and KEGG enrichment analyses indicated that DEGs were primarily enriched in biological processes such as mitotic cell cycle and DNA metabolism, as well as related signaling pathways. Cell cycle analysis demonstrated G2/M phase arrest in the combination group. Clustering analysis of genes enriched in the biological process of “mitotic cell cycle” showed that the majority of these genes were clustered within the “mitosis” category. Immunofluorescence staining revealed multinucleation induced by the combination treatment and the results of RT-qPCR indicated that the combination of drugs could significantly reduce the mRNA levels of genes related to mitosis.

CONCLUSION Schisandrin A combined with low-concentration paclitaxel can inhibit A2780/TAX cell viability and proliferation, induce apoptosis, and suppress migration. The underlying mechanism may involve dysregulation of mitotic processes in A2780/TAX cells.