Resistance to paclitaxel increases the sensitivity to other microenvironmental stresses in prostate cancer cells

Abstract

The microenvironment is central to many aspects of cancer pathobiology and has been proposed to play a role in the development of cancer cell resistant to therapy. To examine the response to microenvironmental conditions, two paclitaxel resistant prostate cancer cell lines (stable and reversible) and one reversible heat resistant cell line were studied. In comparison to their parental cell lines, both paclitaxel resistant cell lines (stable and reversible) were more sensitive to microenvironmental heat, potentially yielding a synergistic therapeutic opportunity. In the two phenotypic cells repopulated after acute heat or paclitaxel treatments, there was an inverse correlation between paclitaxel and heat resistance: resistance to paclitaxel imparted sensitivity to heat; resistance to heat imparted sensitivity to paclitaxel. These studies indicate that as cancer cells evolve resistance to single microenvironmental stress they may be more sensitive to others, perhaps allowing us to design new approaches for prostate cancer therapy.

Stress-Response Protein RBM3 Attenuates the Stem-like Properties of Prostate Cancer Cells by Interfering with CD44 Variant Splicing

“…PC3 and DU145 cells were heated to 43 C or treated with paclitaxel, and then allowed to recover (28). RBM3 expression was found to be significantly lower in the surviving cells than the parental cells ( Fig.…”

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

“…Derivation of OPCT-1 and OPCT-2 has been previously briefly described7071 and the details of these cell lines are also available from Asterand Bioscience. OPCT-1 has been used previously in the literature727374. Briefly, OPCT-1 cell lines are derived from a 68 year old patient (TNM Stage T1cN0M0; Gleason score of 6 [3 + 3]) and OPCT-2 were derived from a 58 year old patient (T2aN0M0 and Gleason score of 5 [2 + 3]) and immortalised via replication-defective retrovirus transferring the transforming HPV16 or HPV18 E6 and E7 genes.…”

Downregulation of cytokeratin 18 is associated with paclitaxel-resistance and tumor aggressiveness in prostate cancer

“…DU145 cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, Shanghai, China) at 37˚C in incubator with humidified air and 5% carbon dioxide. The stable paclitaxel-resistant DU145-TxR cells were generated by culturing DU145 cells with stepwise increasing concentrations of paclitaxel (8,15). The initial culture was at 10 nM paclitaxel (Sigma-Aldrich, St. Louis, MO, USA) for 2 days.…”

“…One of the hallmarks of cancer cell adaption to the microenvironmental stresses, such as chemotherapeutics, heat and radiation, is alterations in the nuclear architecture (6)(7)(8). In concordance with these changes are alterations in nuclear matrix proteins (NMPs) which comprise the structural elements of the nucleus and likely act as a signature for tumorigenesis.…”

“…We have previously established a stable paclitaxel-resistant DU145-TxR cell line from the androgen-independent DU145 cell line, which mimics to a certain extent the progression of paclitaxel-resistance in PCa patients (8,15). In the present study, we aimed to identify differentially expressed protein(s) associated with paclitaxel-resistance by comparing the NMP patterns of DU145-TxR cells with that of DU145 cells and further explore the potential mechanisms involved in the drug resistance, which may help develop novel therapeutic strategies as well as clinically useful biomarker(s) for PCa patients.…”