Human head and neck squamous carcinoma is the 6th most prevalent carcinoma worldwide. Although many novel therapies have been developed, the clinical treatment for patients remains non-ideal. Chloride intracellular channel 4 (CLIC4), one of the seven members of the CLIC family, is a newly found Cl− channel that participates in various biological processes, including cellular apoptosis and differentiation. Accumulating evidence has revealed the significant role of CLIC4 in regulating the apoptosis of different cancer cells. Here, we investigated the functional role of CLIC4 in the apoptosis of HN4 cells, a human head and neck squamous carcinoma cell line. In the present study, we used immunohistochemical staining to demonstrate that the expression level of CLIC4 is elevated in the tissue of human oral squamous carcinoma compared with healthy human gingival tissue. Specific CLIC4 small interfering RNA was used to knockdown the expression of CLIC4. The results showed that knockdown of CLIC4 with or without 100 μM adenosine triphosphate (ATP) treatment significantly increased the expression of Bax, active caspase 3, active caspase 4 and CHOP but suppressed Bcl-2 expression in HN4 cells. Moreover, the results from the TdT-mediated dUTP nick end labeling assay indicated that CLIC4 knockdown induced a higher apoptotic rate in HN4 cells under the induction of ATP. In addition, knockdown of CLIC4 dramatically enhanced ATP-induced mitochondrial membrane depolarization in HN4 cells. Moreover, intracellular Ca2+ measurement revealed that Ca2+ release induced by ATP and thapsigargin, a Ca2+-ATPase inhibitor of the endoplasmic reticulum, was significantly enhanced by the suppression of CLIC4 in HN4 cells. Knockdown of CLIC4 enhanced ATP-induced apoptosis in HN4 cells. Both the pathways of mitochondria and endoplasmic reticulum stress were involved in CLIC4-mediated cell apoptosis. Based on our finding, CLIC4 may be a potential and valuable target for the clinical treatment of head and neck squamous carcinoma.

Tumor suppressor gene p53 plays an important role in the maintenance of the genomic integrity, and mutation in the gene may alter an individual’s susceptibility to various carcinomas. P53 Arg72Pro or codon 72 polymorphism has been indicated to increase the risk of developing certain cancers such as bladder cancer and cervical cancer. Human papillomavirus (HPV) infection has been shown as a risk factor for certain cancers such as cervical cancer and oral cancer as well, and the HPV oncoprotein E6 may induce the degradation of p53 function. However, the association between p53 Arg72Pro polymorphism and the risk of oral cancer with HPV infection remains inconclusive. Therefore, this meta-analysis involving 5,614 participants was performed to investigate the relations among the p53 Arg72Pro polymorphism, HPV infection, and the risk of developing oral cancer. A search of the literature by PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted to identify studies based on the inclusion and exclusion criteria. Odds ratios with 95 % confidence intervals were combined using a random-effect model or a fixed-effect model. The current study was conducted with 13 studies consisting of 2,413 cases and 3,201 controls. Neither overall analysis nor stratified analyses detected any obvious evidence of association between p53 Arg72Pro polymorphism and oral cancer susceptibility in all genetic models. However, a significant association between p53 Arg72Pro polymorphism and the risk of oral cancer with HPV infection was detected in the Arg/Arg vs. Arg/Pro + Pro/Pro model. In the current meta-analysis which used the quantitative data synthesis for the first time, our study demonstrated that p53 Arg72Pro polymorphism together with HPV infection might jointly alter an individual’s susceptibility to the risk of oral cancer. Our results suggested that p53 Arg72Pro polymorphism may partly contribute to the pathogenesis of oral cancer development.

Head and neck squamous cell carcinoma ranks as the sixth most common malignant tumor worldwide, with the majority of cases manifesting as oral squamous cell carcinoma (OSCC). The current clinical standard for treating OSCC consists of surgical resection followed by radiotherapy and chemotherapy. This multimodal approach, however, is associated with substantial morbidity, significant perioperative risk, and frequent systemic toxicities that markedly impair quality of life. Therefore, novel, more effective, and safer treatment strategies are urgently needed. Here, PtTe₂ nanorods were synthesized and encapsulated in sodium alginate (ALG) to form a novel injectable hydrogel for the precise treatment of OSCC. This ALG hydrogel prolongs the intratumoral retention of PtTe₂, ensuring sustained local availability. PtTe₂ exhibits tumor microenvironment-responsive catalytic activity, catalyzing the conversion of hydrogen peroxide into highly toxic hydroxyl radicals via Fenton-like reactions. Moreover, PtTe₂ possesses exceptional photothermal conversion efficiency, enabling precise, light-driven hyperthermia that selectively and effectively ablates tumor cells. By synergistically accelerating the kinetics of Fenton-like reactions through photothermal effects, the generation of reactive oxygen species is substantially amplified, effectively overwhelming the antioxidant defense system and achieving significant antitumor effects. Both in vitro and in vivo experiments demonstrated that the PtTe₂-ALG hydrogel achieved robust antitumor efficacy and excellent biosafety. Transcriptomic analyses revealed significant activation of apoptosis-related signaling cascades, elucidating the molecular mechanism of PtTe₂-based tumor therapy. By combining chemodynamic and photothermal therapy within a single, injectable platform, this work provides a promising, low-toxicity strategy for the clinical management of OSCC.