<b>Protein expression profile related to cisplatin resistance in bladder cancer cell lines detected by two-dimensional gel electrophor</b><b>esis </b>

Abstract

We used a proteomic approach to compare the differentially regulated protein expression profiles of cisplatin-naïve and cisplatin-resistant bladder cancer cell lines to screen candidate molecules related to cisplatin resistance. The cisplatin-resistant cell line T24 was established by the stepwise exposure of T24 cells to up to 40 μM of cisplatin. We performed a comprehensive study of protein expression in bladder cancer cell lines that included cisplatin-naïve (T24) and cisplatin-resistant cells (T24CDDPR) by means of agarose two-dimensional gel electrophoresis followed by analysis of liquid chromatography tandem mass spectroscopy. We identified 25 obviously different spots for T24 and T24 CDDPR. Seven spots had increased expression and 18 spots had decreased expression in T24CDDPR compared to those in T24. Cytoskeletal proteins and enzyme modulators were prominent among differential proteins. Of the 25 proteins, we selected HNRNPA3, PCK2, PPL, PGK1, TKT, SERPINB2, GOT2, and EIF3A for further validation by Western blot. HNRNPA3, PGK1, TKT, and SERPINB2 had more than 1.5-times incremental expression in T24CDDPR compared to that in T24. PCK2 and PPL expressions were decreased less than 20% in T24CDDPR compared to that in T24. The results of 25 new proteins in this study could be valuable and could lead to the development of a new molecular marker.

Prognostic values of transketolase family genes in ovarian cancer

“…These results were consistent with those from previous studies. Taoka et al (45) compared differential protein expression profiles between platinum-naïve and platinum-resistant bladder cancer cell lines to identify the candidate molecules associated with platinum resistance, and revealed that the expression of TKT was increased by 1.5-fold in platinum-resistant bladder cancer compared with that in platinum-naïve cells. Yang et al (31) also demonstrated that silencing of TKT significantly reduced cell viability and increased apoptosis in the presence of platinum via glutathione depletion and reactive oxygen species generation in cervical cancer.…”

High Expression of PQBP1 and Low Expression of PCK2 are Associated with Metastasis and Recurrence of Osteosarcoma and Unfavorable Survival Outcomes of the Patients

“…Interestingly, we noted that the most significantly enriched GO terms and KEGG pathways for genes encoding proteins in the network were related to metabolic dysfunction, suggesting that aberrations in metabolism may play an important role in OS metastasis and recurrence. Previous research has reported that PCK2 downregulation leads to a reduction in energy metabolism and may subsequently decrease susceptibility to chemotherapeutic drugs 53. This may explain why low expression of PCK2 is associated with increased likelihoods of metastasis and recurrence in OS patients.…”

“…Conversely, another study reported that overexpression of PCK2 hindered tumorigenesis and slowed the growth of tumor-repopulating cells growth 52. Moreover, expression of the PCK2 protein gradually decreased in cisplatin-resistant bladder cancer cells compared to levels in cisplatin-naïve cells, and this decrease was dependent on the cisplatin concentration 53.…”

Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer

“…Recently, T24 cells resistant to cisplatin (40 μM) (T24CDDPR) were established and compared with cisplatin-naïve (T24) cells through two-dimensional gel electrophoresis and LC-MASS. PGK1 was 1 of 25 differently overexpressed proteins (>1.5-fold change) in T24CDDPR cells compared with T24 cells [ 107 ]. Wang’s group claimed that, in addition to platinum-based compounds, shikonin can specifically bind to PKM2, but PKM1 does not.…”