Proteomic analysis of the proteins that are associated with the resistance to paclitaxel in human breast cancer cells

Abstract

Cancers frequently develop resistance to paclitaxel but the underlying molecular mechanisms remain to be determined. We have investigated the proteins that are associated with the paclitaxel resistance in human breast cancer MCF-7 cells using proteomic analysis. Paclitaxel resistant human breast cancer MCF-7 cells (MCF-7/P) were established by escalating the concentrations of paclitaxel to drug-sensitive MCF-7 cells (MCF-7/S). The global protein profiles of MCF-7/P and MCF-7/S were compared using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Eleven proteins were upregulated while six proteins were downregulated in MCF-7/P cells. Western blot and real-time PCR analyses showed that the protein and mRNA levels of heterogeneous nuclear ribonucleoprotein (hnRNP C1/C2), SET nuclear oncogene (SET), aspartate aminotransferase (AAT), transgelin-2 (TAGLN2) were increased, while those of nucleoside-diphosphate kinase A (NDKA) were decreased in MCF-7/P cells. Accordingly, knockdown of TAGLN2 by siRNA sensitized MCF-7/P cells to paclitaxel and reduced the multidrug resistance (MDR). Our identification of differential proteins, particularly transgelin-2, provides new insights into the mechanism of MDR to paclitaxel and novel biological targets for breast cancer treatment.

Salvianolic acid A reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating transgelin 2

“…There is strong evidence in the literature of a link between chemoresistance and EMT, which is a critical event in cancer development 22 was also found to be associated with the growth of lung cancer cells 28 . Consistent with these findings, our previous study showed that transgelin 2 was critically involved in the growth of MCF-7/PTX cells 13 transgelin 2 by SAA is likely to be a safer approach for the treatment of breast cancer.…”

“…Our previous study demonstrated that transgelin 2 was ectopically overexpressed in MCF-7/PTX cells 13 property of MCF-7/PTX cells, attenuated N-cadherin and Vimentin, and increased the expression of E-cadherin ( Fig. 5B and 5C).…”

Redox-responsive F127-folate/F127-disulfide bond-D-α-tocopheryl polyethylene glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal of multidrug resistance in tumors

“…The PTX-resistant MCF-7 (MCF-7/PTX) cell line was established as previously described. 34 Culture plates and dishes were obtained from Corning Incorporated (Corning, NY, USA). The culture medium was RPMI 1640, supplemented with 10% FBS, 100 mg/mL streptomycin sulfate, and penicillin 100 IU/mL.…”

Biodegradable mixed MPEG-SS-2SA/TPGS micelles for triggered intracellular release of paclitaxel and reversing multidrug resistance

“…The PTX-resistant MCF-7 (MCF-7/PTX) cell line was established as previously described. 34 Culture plates and dishes were purchased from Corning Incorporated (Corning, NY, USA). Cells were cultured in Roswell Park Memorial Institute (RPMI)-1640 medium, …”