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23 March 2021 Curcumin Enhances the Radiosensitivity of Human Urethral Scar Fibroblasts by Apoptosis, Cell Cycle Arrest and Downregulation of Smad4 via Autophagy
Chun Du, Yongfeng Tian, Wanli Duan, Xin Chen, Wei Ren, Qian Deng
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Abstract

The goals of this study were to determine whether curcumin can radiosensitize human urethral scar fibroblasts (HUSFs) and inhibit the synthesis of collagen, and to explore the molecular mechanism. Here, HUSFs were established and cultured in vitro and cell counting kit-8 (CCK-8) experiment and plate clone formation assay were performed to determine the appropriate concentration of curcumin and radiation dose. The radiosensitization of curcumin was confirmed by plate clone formation assay. Cell cycle distribution was determined by flow cytometry and apoptosis rate by TdT-mediated dUTP nick-end labeling (TUNEL). Western blot was used to detect the levels of collagen I, collagen III, Smad2, Smad3, Smad4, transforming growth factor-β (TGF-β1), Beclin1 and microtubule-associated protein light chain 3 (LC3), as a means of determining the mechanism. Our findings showed that curcumin enhanced radiosensitivity of HUSFs in vitro (sensitization enhancement ratio = 2.030). Furthermore, curcumin and radiation treatments promoted the apoptosis of HUSFs and blocked the cells in G2/M phase. In addition, curcumin combined with radiation inhibited the synthesis of collagen I and collagen III through Smad4 pathway, with possible involvement of autophagy. These results suggest that curcumin could be a radiosensitizer of HUSFs, inhibit the proliferation of HUSFs and suppress fibrosis by downregulation of Smad4 via autophagy.

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Chun Du, Yongfeng Tian, Wanli Duan, Xin Chen, Wei Ren, and Qian Deng "Curcumin Enhances the Radiosensitivity of Human Urethral Scar Fibroblasts by Apoptosis, Cell Cycle Arrest and Downregulation of Smad4 via Autophagy," Radiation Research 195(5), 452-462, (23 March 2021). https://doi.org/10.1667/RADE-20-00239.1
Received: 20 October 2020; Accepted: 15 February 2021; Published: 23 March 2021
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