Doxorubicin‑induced chemoresistance in Duke’s type B colon adenocarcinoma cell line is aggravated in the presence of TGF‑β2 through non‑apoptotic cell death

• Sruthi Sritharan ^[1] ; Nageswaran Sivalingam ^[1]
  1. [1] Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 7, 2024, págs. 1630-1638
• Idioma: inglés
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• Resumen

  • Background The current challenge in clinical cancer treatment is chemoresistance. Colon cells have inherently higher xenobiotic transporters expression and hence can attain resistance rapidly. Increased levels of TGF-β2 expression in patients have been attributed to cancer progression, aggressiveness, and resistance. To investigate resistance progression, we treated doxorubicin (dox) to HT-29 colon adenocarcinoma cells in the presence or absence of TGF-β2 ligand.

    Methods After 1, 3-, and 7-day treatment, we investigated cell proliferation, viability, and cytotoxicity by MTT, trypan blue staining, and lactate dehydrogenase enzyme release. The mechanism of cell death was elucidated by hoechst33342 and propidium iodide dual staining and apoptosis assay. The development of resistance was detected by rhodamine123 efux and P-glycoprotein (P-gp)/MDR1 antibody staining through fuorimetry and fow cytometry. The colony formation ability of the cells was also elucidated.

    Results Inhibition of cell proliferation was noted after day 1, while a signifcant reduction in viability and a signifcant increase in lactate dehydrogenase release was detected after day 3. Reduction of intracellular rhodamine123 levels was detected after day 3 and was signifcantly lower in dox with TGF-β2 treatment compared to dox alone. Increased surface P-gp levels after days 3 and 7 were observed in the treated groups. Hoechst33342/propidium iodide staining and apoptosis assay indicated non-apoptotic cell death. The cells treated with TGF-β2 had higher colony formation ability.

    Conclusions TGF-β2 expression might play a signifcant role in the development of chemoresistance to doxorubicin in Duke’s type B colon adenocarcinoma cell line, HT-29.