Proteomic analysis of multidrug‐resistance mechanisms in adriamycin‐resistant variants of DLKP, a squamous lung cancer cell line

Abstract

Alterations in protein expression associated with adriamycin resistance in a panel of variants derived from the poorly differentiated squamous cell lung carcinoma DLKP were investigated using 2-D DIGE. Of the 80 proteins identified as being differentially expressed, 32 correlated to adriamycin resistance. Twenty-four proteins showed positive correlations with drug resistance, 11 correlated directly with increase in the resistance (including NDPK, RPA2, CCT2, HSP70 and Annexin A1) while 13 proteins (including HNRP K and H1, aldehyde dehydrogenase (ALDH), stomatin and CCT3) increased to a similar level in all drug-resistant variants. Fewer proteins showed an inverse correlation with resistance; two (protein disulphide isomerase (PDI) and HSP70 variant 1) displayed a similar decrease in all variants and six (including prohibitin (PHB) and EIF5A) correlated inversely with resistance. Three proteins (EEF1D, Actin G1 and Annexin 1) correlated with the invasive status of these variants. Some expected targets of adriamycin action showed correlation with resistance including RPA2 (critical for DNA damage repair), while others proteins involved in protection from ROS production (such as GST, peroxiredoxins and thioredoxins) did not. The proteomic analysis revealed a large number of changes in protein expression that may contribute to a more apoptosis-resistant state. Many of these changes could provide novel targets for overcoming resistance.

Comparative proteomic profiling identified sorcin being associated with gemcitabine resistance in non-small cell lung cancer

“…Our proteomic analysis revealed a panel of proteins increased in a gemcitabine-resistant NSCLC cell line compared with its gemcitabine-sensitive control. Among the differently regulated proteins, six proteins (60 kDa heat shock protein, alpha enolase, heat shock cognate 71 kDa protein, protein disulfide isomerase, sorcin, annexin A1) have been found to be related to chemotherapy resistance in previous proteomic studies [13][14][15][16][17][18], and our findings are consistent with most of the previous works (details in Table 1). Furthermore, our study also identified eight gemcitabine-resistance-associated proteins which have not been reported in previous proteomic studies on chemotherapy resistance (details in Table 1).…”

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

“…Table 2 shows that DLKPA is cross-resistant to the taxanes, docetaxel (253-fold) and paclitaxel (258-fold). Its mechanism of resistance is primarily through overexpression of Pgp as previously described (Keenan et al , 2009; Collins et al , 2010; Dunne et al , 2011). While DLKPA overexpresses Pgp, it does not express the MRP1 or BCRP drug resistance pumps (Collins et al , 2010).…”

Dynamic Acclimation to High Light in Arabidopsis thaliana Involves Widespread Reengineering of the Leaf Proteome

“…Using the Progenesis default normalization method, it was found that in the WT, of the 1993 quantified proteins, 251 increased and 369 decreased in abundance. Proteins were considered to have significantly changed in abundance when a p -value of <0.05 or lower was reached, with a minimum fold change of 1.2, a level widely adopted in proteomics experiments (Nissom et al, 2006; Keenan et al, 2009; Serang et al, 2013; Zhang et al, 2016). In the present case, however, using such a normalization arguably gives misleading results.…”