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  • Reduced expression of enolase-1 correlates with high intracellular glucose levels and increased senescence in cisplatin-resistant ovarian cancer cells.

Reduced expression of enolase-1 correlates with high intracellular glucose levels and increased senescence in cisplatin-resistant ovarian cancer cells.

American journal of translational research (2020-05-02)
Yasmarie Santana-Rivera, Robert J Rabelo-Fernández, Blanca I Quiñones-Díaz, Nilmary Grafals-Ruíz, Ginette Santiago-Sánchez, Eunice L Lozada-Delgado, Ileabett M Echevarría-Vargas, Juan Apiz, Daniel Soto, Andrea Rosado, Loyda Meléndez, Fatima Valiyeva, Pablo E Vivas-Mejía
ABSTRACT

Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop a platinum-resistant disease with a poor overall prognosis. The molecular events leading to the cisplatin resistance of ovarian cancer cells are not fully understood. Here, we performed a proteomic analysis to identify protein candidates deregulated in a cisplatin-resistant ovarian cancer cell line (A2780CP20) in comparison to their sensitive counterpart (A2780). Forty-eight proteins were differentially abundant in A2780CP20, as compared with A2780, cells. Enolase-1 (ENO1) was significantly decreased in cisplatin-resistant ovarian cancer cells. Western blots and RT-PCR confirmed our findings. Ectopic ENO1 expression increased the sensitivity of ovarian cancer cells to cisplatin treatment. In contrast, small-interfering (siRNA)-based ENO1 silencing in A2780 cells reduced the sensitivity of these cells to cisplatin treatment. Whereas glucose consumption was lower, intracellular levels were higher in cisplatin-resistant ovarian cancer cells as compared with their cisplatin-sensitive counterparts. Senescence-associated β-galactosidase (β-Gal) levels were higher in cisplatin-resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. β-Gal levels were decreased in ENO1 overexpressed clones. Protein levels of the cell cycle regulators and senescence markers p21 and p53 showed opposite expression patterns in cisplatin-resistant compared with cisplatin sensitive cells. Our studies suggest that decreased expression of ENO1 promotes glucose accumulation, induces senescence, and leads to cisplatin resistance of ovarian cancer cells.

MATERIALS
Product Number
Brand
Product Description

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Anti-CSTB antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
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MISSION® esiRNA, targeting human ENO1
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DL-Glyceraldehyde, ≥90% (GC)
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Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
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ATPA, solid