AUTHOR=Lin Bo , Lu Bing , Hsieh I-yun , Liang Zhen , Sun Zicheng , Yi Yang , Lv Weiming , Zhao Wei , Li Jie 

TITLE=Synergy of GSK-J4 With Doxorubicin in KRAS-Mutant Anaplastic Thyroid Cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00632

DOI=10.3389/fphar.2020.00632

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>Anaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it.</p></sec><sec><title>Methods</title><p>Here, we used different concentrations of GSK-J4 or a combination of GSK-J4 and doxorubicin to treat human Cal-62, 8505C, and 8305C anaplastic thyroid cancer (ATC) cell lines. The <italic>in vitro</italic> experiments were performed using cell viability assays, cell cycle assays, annexin-V/PI binding assays, Transwell migration assays, and wound-healing assays. Tumor xenograft models were used to observe effects <italic>in vivo</italic>.</p></sec><sec><title>Results</title><p>The half maximal inhibitory concentration (IC50) of GSK-J4 in Cal-62 cells was 1.502 μM, and as the dose of GSK-J4 increased, more ATC cells were blocked in the G2-M and S stage. The combination of GSK-J4 and doxorubicin significantly increased the inhibitory effect on proliferation, especially in KRAS-mutant ATC cells <italic>in vivo</italic> (inhibition rate 38.0%) and <italic>in vitro</italic> (suppresses rate Fa value 0.624, CI value 0.673). The invasion and migration abilities of the KRAS-mutant cell line were inhibited at a low concentration (p &lt; 0.05).</p></sec><sec><title>Conclusions</title><p>The combination of GSK-J4 with doxorubicin in KRAS-mutant ATC achieved tumor-suppressive effects at a low dose. The synergy of the combination of GSK-J4 and doxorubicin may make it an effective chemotherapy regimen for KRAS-mutant ATC.</p></sec>