5-FU resistant colorectal cancer cells possess improved invasiveness and βIII-tubulin expression

Abstract

Summary. Background: Elevated βIII-tubulin levels are associated with resistance to a broad spectrum of drugs in different carcinomas and with poor prognosis of various epithelial cancers. 5-Fluorouracil (5-FU) is a widely used standard drug in chemotherapeutic regimens for colorectal cancer treatment, although the resistance to 5-FU is a major obstacle to successful therapy. Aim: The aim of the study was to compare the invasive and adhesion properties and the expression levels of βIII-tubulin in a 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cell line HCT116 and parental cells. Materials and Methods: The 5-FU-resistant cell line was established by continuous stepwise selection with increasing concentrations of 5-FU. Cell viability and properties were evaluated using MTT, adhesion and Transwell invasion assays, respectively. The expression of βIII-tubulin was revealed by immunoblot and immunofluorescence. Results: The derivative line is 25-fold more resistant to 5-FU and characterized by altered cell morphology. Twice as many cells of the 5-FU-resistant line fail to adhere as compared to the parental cell line. 5-FU-resistant cells are characterized by enhanced invasiveness, accompanied with the increased βIII-tubulin expression. In addition, we found that loss of βIII-tubulin expression was correlated with loss of 5-FU resistance. Conclusion: Our results indicate that even though 5-FU does not target microtubules, there appears to be a correlation between βIII-tubulin expression and resistance to 5-FU that is particularly important with regard to invasiveness. These findings indicate a possible contribution of βIII-tubulin to 5-FU resistance in vivo.

Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways

“…5-Fluorouracil (5-FU) is an anti-metabolic antitumor drug, which can inhibit thymine nucleotide synthetase and interfere with DNA synthesis ( Taflin et al, 2021 ). It exerts significant antitumor effect in a variety of tumors ( Akalovich et al, 2021 , Proietti et al, 2021 ). However, the clinical application of 5-FU is facing serious challenges due to the increased drug resistance and the high incidence of adverse reactions ( Vodenkova et al, 2020 ).…”

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

“…Since cancer cells are immortal cells that proliferate abnormally, we correlate adhesive properties and cells’ health status ( Tubiana, 1989 ; Hanahan and Weinberg, 2011 ; Feitelson et al, 2015 ). Therefore, cell proliferation is determined by the MEA’s area covered with adherent cells, assuming a loss in cell adhesion due to the cytotoxic anti-cancer drug 5-FU ( Akalovich et al, 2021 ; Fohlen et al, 2021 ). Our MEA comprises both subcellular resolution ( Hierlemann et al, 2011 ; Viswam et al, 2018 ; Ell, Zeitler, et al, 2023 ) and cellular network studies ( Amin et al, 2017 ; Viswam et al, 2017 ; Angotzi et al, 2018 ; Abbott et al, 2022 ; Cojocaru et al, 2022 ; Emery et al, 2022 ; 2023 ).…”