Depletion of RUVBL2 in Human Cells Confers Moderate Sensitivity to Anticancer Agents

Mayumi Miyamoto Matsubara
2014 Journal of Cancer Science & Therapy  
Many anticancer agents kill cancer cells by inducing lethal damage in DNA, but the capacity of DNA repair of cells reduce the therapeutic efficacy of anticancer agents. RuvB-like (RUVBL) 2 is part of large protein complexes such as TIP60 and INO80 that are involved in chromatin remodeling and DNA damage responses and repair. Relatively few studies have investigated the role of RUVBL2 in the survival of cells after exposure to anticancer agents. Methods: We depleted RUVBL2 in human MRC5-SV cells
more » ... by small interfering (si) RNA and assessed the sensitivity of the cells to chemotherapeutic anticancer agents including cisplatin (cisPt), 2'-deoxy-5-azacytidine (azadC), and mitomycin C (MMC), and to physical DNA-damaging agents including X-rays. Results: The knockdown efficiency with 10 nM siRUVBL2 was 80% on day 3 post-transfection, and knockdown (>65%) persisted on day 6. The cell growth slowed significantly due to depletion of RUVBL2 when compared to mock-and control siRNA-treated cells, indicating that RUVBL2 is essential for the proliferation of cells. The RUVBL2-depleted cells were moderately sensitive to cisPt, azadC, and X-rays. The increase in the sensitivity to MMC was marginal. Conclusion: Depletion of RUVBL2 in cells confers moderate sensitivity to anticancer agents and X-rays, presumably through partial impairment of the homologous recombination repair of DNA double-strand break intermediates formed directly or indirectly by anticancer agents or X-rays. Further studies are necessary to clarify the exact role of RUVBL2 in this process.
doi:10.4172/1948-5956.1000306 fatcat:rmbmx5ufe5bdzagbkyq7lbovei