Enhancing the Radiosensitivity of Colorectal Cancer Cells by Reducing Spermine Synthase Through Promoting Autophagy and DNA Damage

Overview

Journal World J Gastrointest Oncol

Publisher Baishideng Publishing Group

Date 2024 Dec 16

PMID 39678812

Authors

Yu-Bin Guo

Yue-Ming Wu

Zhi-Zhao Lin

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer (CRC), the third most common cancer worldwide, has increasingly detrimental effects on human health. Radiotherapy resistance diminishes treatment efficacy. Studies suggest that spermine synthase (SMS) may serve as a potential target to enhance the radiosensitivity.

Aim: To investigate the association between SMS and radiosensitivity in CRC cells, along with a detailed elucidation of the underlying mechanisms.

Methods: Western blot was adopted to assess SMS expression in normal colonic epithelial cells and CRC cell lines. HCT116 cells were transfected with control/SMS-specific shRNA or control/pcDNA3.1-SMS plasmids. Assessments included cell viability, colony formation, and apoptosis MTT assays, colony formation assays, and flow cytometry. Radiosensitivity was studied in SMS-specific shRNA-transfected HCT116 cells post-4 Gy radiation, evaluating cell viability, colony formation, apoptosis, DNA damage (comet assays), autophagy (immunofluorescence), and mammalian target of rapamycin (mTOR) pathway protein expression (western blot).

Results: Significant up-regulation of SMS expression levels was observed in the CRC cell lines. Upon down-regulation of SMS expression, cellular viability and colony-forming ability were markedly suppressed, concomitant with a notable increase in apoptotic indices. Furthermore, attenuation of SMS expression significantly augmented the sensitivity of HCT116 cells to radiation therapy, evidenced by a pronounced elevation in levels of cellular DNA damage and autophagy. Importantly, down-regulation of SMS corresponded with a marked reduction in the expression levels of proteins associated with the mTOR signaling pathway.

Conclusion: Knocking down SMS attenuates the mTOR signaling pathway, thereby promoting cellular autophagy and DNA damage to enhance the radiosensitivity of CRC cells.

Citing Articles

PI3K/AKT/mTOR Targeting in Colorectal Cancer Radiotherapy: A Systematic Review.

Mousavikia S, Darvish L, Firouzjaei A, Toossi M, Azimian H J Gastrointest Cancer. 2025; 56(1):52.

PMID: 39849185 DOI: 10.1007/s12029-024-01160-1.

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