Radiosensitizing effects of curcumin alone or combined with GLUT1 siRNA on laryngeal carcinoma cells through AMPK pathway‐induced autophagy

Abstract

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy‐related proteins in LC and that curcumin suppressed radiation‐mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6‐amino‐3‐methypourine (3‐MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3‐MA inhibited curcumin and GLUT1 siRNA‐mediated non‐apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3‐MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP‐activated protein kinase‐mTOR‐serine/threonine‐protein kinase‐Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

Chitosan-Based Glycolipid Conjugated siRNA Delivery System for Improving Radiosensitivity of Laryngocarcinoma

“…As reported by some previous studies [20,21], there is also high expression of GLUT-1 in laryngocarcinoma, and the expression of GLUT-1 is related to the radioresistance of laryngocarcinoma. Thus, inhibiting the expression of GLUT-1 can improve the radiosensitivity of laryngocarcinoma.…”

Effect of Glut‐1 and HIF‐1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway

“…Hypoxia induces the stabilization of HIF‐1α, which is associated with radiotherapy resistance in head and neck carcinoma 31 . Our previous research indicated a significant association between Glut‐1 and radioresistance in laryngeal carcinoma 20‐22,32,33 . Furthermore, HIF‐1α and Glut‐1 double knockout using the CRISPR/CAS9 system showed synergistic regulation of biological behaviour in laryngeal carcinoma cells 23 .…”

“…31 Our previous research indicated a significant association between Glut-1 and radioresistance in laryngeal carcinoma. [20][21][22]32,33 Furthermore, HIF-1α and Glut-1 double knockout using the CRISPR/CAS9 system showed synergistic regulation of biological behaviour in laryngeal carcinoma cells. 23 Glut-1 antisense oligodeoxynucleotides facilitated the response to radiotherapy in laryngeal carcinoma tissue via autophagy regulation.…”

Glucose transporters: Important regulators of endometrial cancer therapy sensitivity

“…It might function as a novel anticancer drug to assist chemoradiotherapy by inhibiting a site overlapping the cytochalasin B of GLUT1 and metabolism-related enzymes (129)(130)(131). In some studies concerning cervical cancer, the theory that curcumin enhances radiosensitivity by inhibiting GLUT1-induced PI3K/AKT/mTOR pathway or MAPK/mTOR/ ULK1 pathway and subsequently activating autophagy has also been confirmed (121,125,132). Therefore, we speculate that there may be a similar mechanism in EC.…”

“…A large amount of data indicate that the anti-radiosensitivity in EC refers to PI3K/PTEN/AKT/mTOR signaling pathway, MAPK signaling pathway, and NF-kB signaling pathway; each of them is directly or indirectly involved in tumor radioresistance and GLUT1-induced malignant processes that include proliferation, angiogenesis, and EMT in EC (124,125). It is clear that either upstream elements' inhibitors of these significant pathways or inhibitors of GLUT1 itself should play a therapeutic role in the radio-resistance of EC.…”