Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein   全文下載

Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein

"This study demonstrated for the first time that curcumin effectively inhibits the growth of triple-negative breast cancer(TNBC) tumors by inhibiting the expression of salt-induced kinase-3 (SIK3) protein in patient-derived xenograftedtumor mice (TNBC-PDX). For TNBC patients, chemotherapy is the only option for postoperative adjuvant treatment. Inthis study, we detected the SIK3 mRNA expression in paired-breast cancer tissues by qPCR analysis. The results revealedthat SIK3 mRNA expression was significantly higher in tumor tissues when compared to the normal adjacent tissues(73.25 times, n¼183). Thus, it is proposed for the first time that the antitumor effect induced by curcumin by targetingSIK3 can be used as a novel strategy for the therapy of TNBC tumors. In vitro mechanism studies have shown thatcurcumin (>25 mM) inhibits the SIK3-mediated cyclin D upregulation, thereby inhibiting the G1/S cell cycle andarresting TNBC (MDA-MB-231) cancer cell growth. The SIK3 overexpression was associated with increased mesenchymalmarkers (i.e., Vimentin, a-SMA, MMP3, and Twist) during epithelialemesenchymal transition (EMT). Our resultsdemonstrated that curcumin inhibits the SIK3-mediated EMT, effectively attenuating the tumor migration. Forclinical indications, dietary nutrients (such as curcumin) as an adjuvant to chemotherapy should be helpful to TNBCpatients because the current trend is to shrink the tumor with preoperative chemotherapy and then perform surgery. Inaddition, from the perspective of chemoprevention, curcumin has excellent clinical application value."