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Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer
Ruo-Fei Sun1,2, Na He1,2, Geng-Yuan Zhang1,2
1Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.
Background:
Novel therapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15- IN-1 and KIF11 inhibitor ispinesib in GC.
Methods:
We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo.
Results:
KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo.
Conclusion:
This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.
Insights
Combining KIF11 and KIF15 inhibitors shows promise for gastric cancer (GC) treatment. This novel strategy targets key proteins involved in cell division, offering a potential new therapeutic avenue for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Gastric cancer (GC) requires novel therapeutic strategies for improved outcomes.
- Kinesin family members KIF11 and KIF15 are crucial for bipolar spindle assembly and chromosome segregation.
- Their cooperative function suggests a potential therapeutic target in GC.
Purpose of the Study:
- To evaluate the combined therapeutic effect of KIF15 inhibitor KIF15-IN-1 and KIF11 inhibitor ispinesib in gastric cancer.
- To investigate the role of KIF11 and KIF15 in GC cell proliferation and sensitivity to inhibition.
Main Methods:
- Validated KIF11 and KIF15 expression in GC tissues via immunohistochemistry and immunoblotting.
- Determined the impact of KIF11 or KIF15 knockout on GC cell proliferation.
- Investigated the synergistic effects of KIF11 and KIF15 inhibitors in vitro and in vivo.
Main Results:
- KIF11 and KIF15 were overexpressed in GC tissues compared to normal tissues.
- Knockout of KIF11 or KIF15 reduced GC cell proliferation and clonogenic potential.
- Combined inhibition of KIF11 and KIF15 demonstrated synergistic antitumor effects in vitro and in vivo.
Conclusions:
- Combined inhibition of KIF11 and KIF15 represents a potential effective therapeutic strategy for gastric cancer.
- Targeting KIF11 and KIF15 offers a novel approach to enhance GC treatment efficacy.
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