Abstract
BackgroundAnaplastic thyroid cancer is the most aggressive thyroid cancer and has a poor prognosis. At present, there is no effective treatment for it.MethodsHere, 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.ResultsThe 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).ConclusionsThe 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.
Highlights
The prognosis of anaplastic thyroid cancer (ATC) patients is poor, which have a median survival of 3–12 months (Subbiah et al, 2018; Lin et al, 2019)
The antiproliferative effect of GSK-J4 and doxorubicin on ATC cells was measured by a cell viability assay
The data indicated that GSK-J4 efficiently inhibited the proliferation of ATC cells
Summary
The prognosis of anaplastic thyroid cancer (ATC) patients is poor, which have a median survival of 3–12 months (Subbiah et al, 2018; Lin et al, 2019). Several studies have shown that the combination of surgery, radiation therapy with chemotherapy (such as doxorubicin), might improve the 1-year OS to more than 40%(Baek et al, 2017; Prasongsook et al, 2017; Fan et al, 2020). Targeted therapy is another possible option, especially for patients with BRAF V600E mutation.
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