Research On Nrf2Promoted Proliferation In Glioma Cells

Background and Objective:Glioma is the most common intracranial malignant tumor, with a high recurrence rate and a low cure rate, which shows serious harm to human health. Therefore, to clarify mechanisms responsible for glioma pathogenesis and to find new biomarkers and therapeutic targets to improve the therapeutic effect has become a major issue to be solved. In resent years, modulation of metabolism in cancer cells has been focused. Nrf2, a key regulator for the maintenance of redox homeostasis, has been shown to contribute to malignant phenotypes of cancers including aggressive proliferation. In the present study, we compared the expression of Nrf2in U87glioma cells. Then we observed the function of Nrf2in glioma cells and explore the possible molecular mechanism.Methods:(1) Real-Time PCR was used to examine the expression pattern of Nrf2in U87glioma cells;(2) Design Antisense oligonucleotide fragments (ASOs) specifically targetting to Nrf2and transfected U87cells with Lippofectamine2000and western blot was used to determine the effect of Nrf2knockdown. Then, MTS assay was used to observe the effect or Nrf2konckdown on proliferation and sensitivity to VM-26,(3) Real-Time PCR and western blot were used to determine the expression of G6PD, PGD and TKT after Nrf2knockdown in U87cells;(4) Design Antisense oligonucleotide fragments specifically targetting to G6PD and TKT respectively, and transfected U87cells with Lippofectamine2000and western blot was used to determine the effect of ASOs respectively. Then, MTS assay was used to observe the effect of G6PD and TKT co-konckdown on proliferation and sensitivity to VM-26Results:(1) the expression of Nrf2in mRNA level in U87cells was with a abundant pattern, and the designed ASO could significantly inhibit Nrf2expression in U87cells;(2) Nrf2knockdown inhibited U87cells proliferation and enhanced the sensitivity of U87cells to VM-26, and Nrf2knockdown also downregulated G6PD, PGD and TKT expression;(3) co-knockdown of G6PD and TKT significantly inhibited U87cells proliferation and improved the sensitivity to VM-26.Conclusion:(1) Nrf2expression in glioma is intensely related with cell proliferation and chemotherapy efficiency;(2) Nrf2exerts its role in glioma cells mostly via modulating the expression of G6PD and TKT.