Paclitaxel and cisplatin inhibit the proliferation of nasopharyngeal cancer stem cells and promote apoptosis via the Wnt/beta-catenin pathway / 中国组织工程研究

ABSTRACT

BACKGROUND:Cancer stem cel s have self-renewal ability and can differentiate into new tumors. Cancer stem cel s are the source of tumor formation and recurrence, and they can make tumors insensitive to radiotherapy and chemotherapy. OBJECTIVE:To explore the effect of paclitaxel plus cisplatin on the proliferation and apoptosis of nasopharyngeal cancer stem cel s (NPCSCs) and involved signal pathways. METHODS:NPCSCs were sorted by immunomagneticbeads and were treated with paclitaxel, cisplatin or their combination. The expression of caspase-3, activated caspase-3 and Bcl-2, which are related to apoptosis, was determined by western blot. The expression ofβ-catenin and its downstream proto-oncogene, c-myc, was also determined by western blot. The activity of the Wnt/β-catenin pathway was inhibited by knocking downβ-catenin expression orβ-catenin inhibitor XAV939. Proliferation and apoptosis of NPCSCs were detected by MTT and flow cytometry, respectively. RESULTS AND CONCLUSION:Either paclitaxel or cisplatin could inhibit proliferation and induce apoptosis of NPCSCs. The expression of apoptosis marker, activated caspase-3, was increased and the expression of the inhibitor of apoptosis, Bcl-2, was declined. Combined use of paclitaxel and cisplatin had synergistic effect when used together. Either paclitaxel or cisplatin could inhibit the expression ofβ-catenin and c-myc, suppressed the proliferation and induced the apoptosis of NPCSCs by inhibiting the activity of Wnt/β-catenin pathway. These results indicate that the combined use of paclitaxel and cisplatin may inhibit the proliferation of NPCSCs and promote apoptosis via the Wnt/β-catenin pathway.