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

Bo Lin, Bing Lu, I. Yun Hsieh, Zhen Liang, Zicheng Sun, Yang Yi, Weiming Lv*, Wei Zhao, Jie Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article number632
JournalFrontiers in Pharmacology
StatePublished - May 13 2020
Externally publishedYes


  • GSK-J4
  • KRAS-mutant
  • anaplastic thyroid cancer
  • epigenetics
  • synergistic action

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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