Radiotherapy is an effective therapeutic strategy in esophageal squamous cell carcinoma (ESCC). However, acquired radioresistance of cancer cells leads to radiotherapy failure. The present study aimed to investigate the mechanisms of the effect of high mobility group box 1 (HMGB1) on the radiation sensitivity of ESCC. Small interfering RNA (si) transfection was used to generate three groups of TE-1 cells (TE-1, negative control and TE-1+siHMGB1), and the protein expression levels of HMGB1 in TE-1 cells were detected by western blotting. These groups of TE-1 cells were irradiated with different doses (0, 2, 4, 6 and 8 Gy) of X-rays after transfection. Subsequently, the viability of TE-1 cells was detected using an MTT assay, and the survival fraction of TE-1 cells was observed using a colony formation assay. The apoptotic rate, reactive oxygen species (ROS) content and levels of phosphorylated (p)-histone H2AX at S139 (p-γH2AX) of the cells were detected by flow cytometry. The alterations in mRNA expression levels of nicotinamide adenine nucleotide phosphate oxidase (NOX)1 and NOX5 were detected by reverse transcription-quantitative PCR, while the changes in protein levels of caspase-3, poly(ADP-ribose) polymerase, p-p38, p-ERK1/2 and p-JNK were detected by western blotting. The results revealed that HMGB1 knockdown significantly decreased cell viability, and the apoptosis rate of TE-1 cells transfected with siHMGB1 combined with radiation treatment was increased compared with that in cells with either siHMGB1 transfection or radiation treatment alone. HMGB1 knockdown increased nicotinamide adenine nucleotide phosphate oxidase-mediated ROS production and induced DNA damage via the MAPK signaling pathway, which may promote apoptosis and radiosensitivity after radiation in TE-1 cells. In conclusion, targeting HMGB1 may represent a promising strategy to increase the efficacy of radiation therapy for ESCC.

As a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

Background This study aimed to explore the clinical efficacy and safety of a modified FOLFOX6 (oxaliplatin + leucovorin + 5-fluorouracil (mFOLFOX6) plus bevacizumab regimen after deep hyperthermia in KRAS/NRAS/BRAFV600E mutant advanced colorectal cancer. Methods A total of 80 KRAS/NRAS/BRAF V600E mutant colorectal cancer patients treated at our hospital were selected as research subjects. According to the random number table method, patients were divided into a control group (mFOLFOX6 plus bevacizumab) and a combination group (mFOLFOX6 plus bevacizumab after deep hyperthermia treatment), with 40 patients in each group. After six cycles of treatment, the objective response rate (ORR), disease control rate (DCR), levels of serum tumor markers carcinoembryonic antigen (CEA), vascular epidermal growth factor (VEGF), Karnofsky performance status (KPS) scores, and the occurrence of adverse reactions were compared between the two groups. Results After six cycles of treatment, the ORR in the combination group was higher than that in the control group, but the difference was not statistically significant (P > 0.05). The DCR in the combination group was significantly higher than that in the control group (P < 0.05). The serum CEA levels in the control and combination groups after treatment were significantly lower than those before treatment, and the serum CEA and VEGF levels in the combination group were significantly lower than those in the control group (all P < 0.001). The KPS scores in both groups after treatment were higher than those before treatment, and the KPS scores in the combination group after treatment were significantly higher than those in the control group (all P < 0.001). The incidence of fatigue in the combination group was significantly lower than that in the control group (P < 0.05). Conclusions mFOLFOX6 plus bevacizumab after deep hyperthermia is effective in KRAS/NRAS/ BRAFV600E mutant advanced colorectal cancer patients, which can effectively improve their quality of life, and the adverse reactions are controllable and tolerable.