Synergy of GSK-J4 With Doxorubicin in KRAS-Mutant Anaplastic Thyroid Cancer
Bo Lin1, Bing Lu2, I-Yun Hsieh1
1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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.
Insights
The combination of GSK-J4 and doxorubicin effectively suppresses anaplastic thyroid cancer (ATC) cell proliferation, invasion, and migration, particularly in KRAS-mutant forms. This synergistic chemotherapy offers a promising new treatment strategy for aggressive ATC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Anaplastic thyroid cancer (ATC) is highly aggressive with limited treatment options.
- Current therapies for ATC lack efficacy, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of GSK-J4, alone and in combination with doxorubicin, against anaplastic thyroid cancer (ATC) cell lines.
- To investigate the anti-proliferative, anti-migratory, and anti-invasive effects of this combination therapy.
Main Methods:
- Utilized human ATC cell lines (Cal-62, 8505C, 8305C) for in vitro studies.
- Performed cell viability, cell cycle, apoptosis, migration, and wound-healing assays.
- Assessed therapeutic effects in vivo using tumor xenograft models.
Main Results:
- GSK-J4 demonstrated dose-dependent inhibition of ATC cell proliferation, causing cell cycle arrest.
- The combination of GSK-J4 and doxorubicin significantly enhanced anti-proliferative effects in both in vitro and in vivo models, especially in KRAS-mutant ATC.
- GSK-J4 at low concentrations inhibited invasion and migration in KRAS-mutant ATC cell lines.
Conclusions:
- Combination therapy with GSK-J4 and doxorubicin exhibits significant tumor-suppressive effects in KRAS-mutant ATC.
- This synergistic drug combination represents a potential effective chemotherapy regimen for KRAS-mutant anaplastic thyroid cancer.
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