Oral squamous cell carcinoma (OSCC) is a very aggressive malignancy, and 50% of patients who receive curative treatment die from the disease or related complications within 5 years. Epigallocatechin‐3‐gallate (EGCG) is the most abundant bioactive ingredient of tea polyphenols in green tea and has anticancer properties. Here, we evaluated the preclinical efficacy of EGCG combined with vincristine sulfate (VCR) on the growth, angiogenic activity and vascular endothelial growth factor (VEGF) expression in xenograft nude mice inoculated with KBV200 cells. Compared with VCR alone, the combined use of EGCG and VCR strongly inhibited tumour growth and angiogenesis ( P < 0.01). VEGF mRNA and protein levels were lower in the KBV200 xenograft group treated with the combined regime ( P < 0.01) than those in the VCR alone group. EGCG sensitises multidrug‐resistant OSCC to VCR, and this may occur through the inhibition of angiogenesis via VEGF down‐regulation.

Patients with advanced-stage or treatment-resistant colorectal cancer (CRC) benefit less from traditional therapies; hence, new therapeutic strategies may help improve the treatment response and prognosis of these patients. Ferroptosis is an iron-dependent type of regulated cell death characterized by the accumulation of lipid reactive oxygen species (ROS), distinct from other types of regulated cell death. CRC cells, especially those with drug-resistant properties, are characterized by high iron levels and ROS. This indicates that the induction of ferroptosis in these cells may become a new therapeutic approach for CRC, particularly for eradicating CRC resistant to traditional therapies. Recent studies have demonstrated the mechanisms and pathways that trigger or inhibit ferroptosis in CRC, and many regulatory molecules and pathways have been identified. Here, we review the current research progress on the mechanism of ferroptosis, new molecules that mediate ferroptosis, including coding and non-coding RNA; novel inducers and inhibitors of ferroptosis, which are mainly small-molecule compounds; and newly designed nanoparticles that increase the sensitivity of cells to ferroptosis. Finally, the gene signatures and clusters that have predictive value on CRC are summarized.

Background: Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy sensitivity. This study aimed to identify lncRNAs related to oxaliplatin sensitivity and predict the prognosis of CRC patients underwent oxaliplatin-based chemotherapy.Methods: Data from the Genomics of Drug Sensitivity in Cancer (GDSC) was used to screen for lncRNAs related to oxaliplatin sensitivity. Four machine learning algorithms (LASSO, Decision tree, Random-forest, and support vector machine) were applied to identify the key lncRNAs. A predictive model for oxaliplatin sensitivity and a prognostic model based on key lncRNAs were established. The published datasets, and cell experiments were used to verify the predictive value.Results: A total of 805 tumor cell lines from GDSC were divided into oxaliplatin sensitive (top 1/3) and resistant (bottom 1/3) groups based on their IC50 values, and 113 lncRNAs, which were differentially expressed between the two groups, were selected and incorporated into four machine learning algorithms, and seven key lncRNAs were identified. The predictive model exhibited good predictions for oxaliplatin sensitivity. The prognostic model exhibited high performance in patients with CRC who underwent oxaliplatin-based chemotherapies. Four lncRNAs, including C20orf197, UCA1, MIR17HG, and MIR22HG, displayed consistent responses to oxaliplatin treatment in the validation analysis.Conclusion: Certain lncRNAs were associated with oxaliplatin sensitivity and predicted the response to oxaliplatin treatment. The prognostic models established based on the key lncRNAs could predict the prognosis of patients given oxaliplatin-based chemotherapy.

ID 14447 Poster Board 46 Aims: Although sorafenib benefits patients with advanced hepatocellular carcinoma (HCC), its clinical efficacy is restricted by drug resistance. The pathogenesis of multisystem tumors is closely related to mitochondrial function, and anticancer drug research has also made significant progress in autophagy, but the regulatory role of mitochondria in the etiology and pharmacology of liver cancer remains unclear. To this end, we focused on the mitochondrial protein Nix (aka BNIP3L, BCL2/adenovirus E1B interacting protein 3-like), hypothesizing that induction of Nix-activated autophagy might represent a mechanism of sorafenib resistance. Methods: We constructed two sorafenib-resistant HCC cell models (HepG2-SR, Huh7-SR) using the concentration-ascending method. Short hairpin RNA was used to knock down the expression of Nix in drug-resistant strains, and the consequences of autophagy signals and drug-resistant cells were observed. The correlation between Nix, autophagy and sorafenib resistance was mainly verified by western blot, IHC, qRT-PCR, CCK8 assay, and flow cytometry. Results: Nix is overexpressed in liver cancer tissues and HCC lines resistant to sorafenib. In addition, the expression level of Nix was dose-dependent and positively correlated with Sorafenib resistance. Inhibiting the expression of Nix in drug-resistant strains can enhance its sensitivity to sorafenib. Furthermore, we showed that autophagy was activated in association with Nix-associated sorafenib resistance and was stopped by Nix knockdown and autophagy inhibitor. Conclusion: Mitochondrial protein Nix regulated sorafenib resistance through autophagy in HCC, proving that autophagy is a cytoprotective mechanism mediating tumor drug resistance. The connection between Nix, autophagy and sorafenib resistance is first described in this study. These findings are significant as they suggest that the combination of targeting NIX therapy and autophagy provides new insights and strategies for the treatment of HCC. This study was supported by the National Natural Science Foundation of China (NO.81860654); the Guangxi Portal Hypertension Key Laboratory Construction Project (NO. ZZH2020006); Guangxi Digestive Disease Clinical Medical Research Center Construction Project (AD17129027).