KIF2C promotes doxorubicin resistance in ovarian cancer cells and increases cancer cell glycolysis by upregulating PKM2

Ovarian cancer stands as one of the most frequently diagnosed malignant tumors among women. Doxorubicin (DOX), a potent anthracycline chemotherapeutic agent, is widely used in the treatment of ovarian cancer. However, resistance to DOX remains a significant challenge. Kinesin family member 2C (KIF2C), a member of the Kinesin-13 family, has been associated with various cancers, but its specific involvement in the resistance of ovarian cancer to DOX remains to be elucidated. This study investigates the role of KIF2C in ovarian cancer DOX resistance. Through meticulous experimentation, we successfully constructed two DOX-resistant ovarian cancer cell lines and found that KIF2C was overexpressed in these cells, promoting cell growth. By silencing KIF2C, we were able to re-sensitize the DOX-resistant cells to the drug and significantly impair their migratory capabilities. Our mechanistic studies revealed that KIF2C upregulates the expression of pyruvate kinase isozyme type M2 (PKM2), thereby enhancing glycolysis—a key metabolic pathway—in DOX-resistant ovarian cancer cells. In summary, KIF2C contributes to DOX resistance and enhances glycolysis in ovarian cancer cells by upregulating PKM2, suggesting that KIF2C may serve as a promising therapeutic target for circumventing drug resistance in ovarian cancer treatments.

Ovarian cancer; Doxorubicin (DOX); KIF2C; Glycolysis; PKM2

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