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=Background

Anaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it.

Methods

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 in vitro 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 in vivo.

Results

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 in vivo (inhibition rate 38.0%) and in vitro (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 < 0.05).

Conclusions

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.