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Toll\u2010like receptor 3 (TLR3) activation promotes IFN\u2010\u03b2 production, which induces apoptosis and impairs proliferation in some cancer cells. Herein, we tested whether the TLR3 agonist polyinosinic: polycytidylic acid (poly I:C) can improve chemotherapeutic efficacy in paclitaxel (PTX) resistant cell lines. Human colon cancer cell lines HCT116, SW620, HCT\u20108 (sensitive to PTX), and HCT\u20108\/PTX (resistant to PTX) were treated with poly I:C and the cell viability was measured. Results showed that poly I:C specifically impaired the cell viability of HCT\u20108\/PTX by simultaneously promoting cell apoptosis and inhibiting cell proliferation. In addition, when TLR3 was overexpressed in HCT\u20108\/PTX cells, we found that TLR3 contributed to the production of IFN\u2010\u03b2 that reduced cell viability, and poly I:C preferentially activated the TLR3\u2010UNC93B1 signaling pathway to mediate this effect. Moreover, cotreatment of poly I:C and PTX acted synergistically to induce cell apoptosis of HCT\u20108\/PTX via upregulating the expression of TLR3 and its molecular chaperone UNC93B1, assisting in the secretion of IFN\u2010\u03b2. Notably, a combination of poly I:C and PTX synergistically inhibited the PTX\u2010resistant tumor growth in vivo without side effects. In conclusion, our studies demonstrate that poly I:C reinforces the potency of cytotoxic chemotherapeutics in PTX\u2010resistant cell line through the TLR3\u2010UNC93B1\u2010IFN\u2010\u03b2 signaling pathway, which supplies a novel mechanism of poly I:C for the chemotherapy sensitizing effect in a PTX\u2010resistant tumor.<\/jats:p>","DOI":"10.1002\/jcp.27459","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T05:12:16Z","timestamp":1541135536000},"page":"7051-7061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Toll\u2010like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3\u2010UNC93B1\u2010IFN\u2010\u03b2 signaling axis in paclitaxel\u2010resistant colon cancer"],"prefix":"10.1002","volume":"234","author":[{"given":"Jiaojiao","family":"Zhao","sequence":"first","affiliation":[{"name":"Division of Immunology The State Key Laboratory of 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