Exosomes derived from Taxol-resistant nasopharyngeal carcinoma (NPC) cells transferred DDX53 to NPC cells and promoted cancer resistance to Taxol.

F Yuan, Z-F Zhou

European review for medical and pharmacological sciences 2021 Jan

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Nasopharyngeal carcinoma (NPC) is a common cancer with high incidence in Southern China. Taxol is one of the first-line chemotherapeutic drugs for treating NPC; however, Taxol resistance has become the main difficulty for clinical treatment and the mechanisms remain not fully understood. In this study, we mainly focus on exploring whether exosomes from Taxol-resistant NPC cells played some roles in the resistance and progression of NPC. Taxol was used to treat NPC cell line CNE1 and Taxol-resistant NPC cell line CNE1-TR cells to measure cell viability and IC50 by CCK-8 assay. Exosomes from these two cells were extracted and identified by transmission electron microscopy (TEM), and special protein markers were determined by Western blot (WB) assay. Real-time PCR was performed to detect levels of mRNAs in exosomes, CNE1 and CNE1-TR cells. WB was performed to detect protein levels. The p-DDX53 and si-DDX53 were constructed and cloned into cells, resulted with DDX53 overexpression and inhibition, then resistant associated protein levels and IC50 were measured. Finally, GW4869, an inhibitor to block exosome secretion, was used to verify that the exosomes derived from CNE1-TR cells transferred DDX53 to CNE1 cells and contributed to promote NPC resistance. We found that the IC50 to Taxolin CNE1-TR was much higher than that in CNE1 cells and DDX53 was highly expressed in Taxol-resistant CNE1-TR cells. Furthermore, exosomes were successfully extracted and determined, showing high levels of DDX53 and MDR1. Thus, they could promote cell resistance for CNE1 after adding CNE1-TR exosomes into CNE1 cells. Moreover, DDX53 overexpression increased the IC50 and upregulated MDR1 in CNE1 cells, while DDX53 inhibition showed the opposite results. In addition, the DDX53 inhibition decreased the IC50 and repressed MDR1 in CNE1-TR cells. Besides, blocking exosome released from CNE1-TR by using GW4869 treatment significantly repressed the levels of DDX53 and MDR1, and the IC50 of CNE1 cells was reversed. Finally, the increased levels of MDR1 were significantly reversed following with adding DDX53 si-DDX53-CNE1-TR exosomes, and the increased IC50 to Taxol was obviously reversed. This study firstly discovered that DDX53 was highly expressed in Taxol-resistant NPC cells, which could be transferred into normal NPC cells via exosome secretion. The transferred DDX53 could upregulate the expression of MDR1 in NPC cells to promote the resistant capacity to Taxol, which provided a novel insight for understanding NPC and might be a potential therapeutic target for NPC.

Citation

F Yuan, Z-F Zhou. Exosomes derived from Taxol-resistant nasopharyngeal carcinoma (NPC) cells transferred DDX53 to NPC cells and promoted cancer resistance to Taxol. European review for medical and pharmacological sciences. 2021 Jan;25(1):127-138