Immune checkpoints expressed on tumor cells may suppress the cytotoxicity of tumor-infiltrating lymphocytes (TILs) via interaction with their ligands. In the present study, checkpoint proteins and ligands, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cluster of differentiation (CD)155 and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) were systematically analyzed in patients with small cell lung cancer (SCLC). Furthermore their clinicopathological features and survival rates were investigated. Immunohistochemistry was performed in order to analyze the expression of PD-L1, CD155, PD-1 and TIGIT in 60 patients with SCLC, and survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. It was reported that CD155/TIGIT and PD-L1/PD-1 were highly expressed on tissues of surgically resected SCLC. High expression levels of PD-L1, CD155 or PD-L1+CD155 were significantly associated with shorter survival. However, high expression levels of PD-1 or TIGIT exhibited no obvious association with shorter survival time. Moreover, patients with SCLC in whom PD-L1 and CD155 levels were highly expressed had the shortest survival rate. Multivariate survival analysis revealed that highly expressed PD-L1 [hazard ratio (HR)=2.55, 95% confidence interval (CI)=1.18–5.51, P=0.017] and CD155 (HR=2.40, 95% CI=1.05–5.50, P=0.038) were independent prognostic factors for overall survival (OS) time in SCLC. In addition, it was reported that TIGIT and PD-1, the receptors of CD155 and PD-L1, respectively, were also constitutively expressed on CD8 + TILs and tumor cells in SCLC. High expression levels of PD-L1 and CD155 were independent prognostic factors for OS time in patients with SCLC.

Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown. The results presented in this research demonstrated that OPN inhibited SIRT1 expression and promoted NF-κB p65 acetylation in NSCLC cell lines (A549 and NCI-H358). In this article, overexpression of SIRT1 was induced by infection of SIRT1-overexpressing lentiviral vectors. The overexpression of SIRT1 protected NSCLC cells against OPN-induced NF-κB p65 acetylation and epithelial-mesenchymal transition (EMT), as indicated by the reduction of OPN-induced changes in the expression levels of EMT-related markers and cellular morphology. Furthermore, SIRT1 overexpression significantly attenuated OPN-induced cell proliferation, migration and invasion. Moreover, overexpression of SIRT1 inhibited OPN-induced NF-κB activation. As OPN induced NSCLC cell EMT through activation of NF-κB signaling, OPN-induced SIRT1 downregulation may play an important role in NSCLC cell EMT via NF-κB signaling. The results suggest that SIRT1 could be a tumor suppressor to attenuate OPN-induced NSCLC progression through the regulation of NF-κB signaling.

Colorectal cancer (CRC) is one of the most commonly diagnosed and deadly malignancies worldwide. The incidence of CRC has been increasing, especially in young people. Although great advances have been made in managing CRC, the prognosis is unfavorable. Numerous studies have shown that berberine (BBR) is a safe and effective agent presenting significant antitumor effects. Nevertheless, the detailed underlying mechanism in treating CRC remains indistinct. In this review, we herein offer beneficial evidence for the utilization of BBR in the management and treatment of CRC, and describe the underlying mechanism(s). The review emphasizes several therapeutic effects of BBR and confirms that BBR could suppress CRC by modulating gene expression, the cell cycle, the inflammatory response, oxidative stress, and several signaling pathways. In addition, BBR also displays antitumor effects in CRC by regulating the gut microbiota and mucosal barrier function. This review emphasizes BBR as a potentially effective and safe drug for CRC therapy.

The incidence and mortality of colorectal cancer (CRC) have been markedly increasing worldwide, causing a tremendous burden to the healthcare system. Therefore, it is crucial to investigate the risk factors and pathogenesis of CRC. Cholecystectomy is a gold standard procedure for treating symptomatic cholelithiasis and gallstone diseases. The rhythm of bile acids entering the intestine is altered after cholecystectomy, which leads to metabolic disorders. Nonetheless, emerging evidence suggests that cholecystectomy might be associated with the development of CRC. It has been reported that alterations in bile acid metabolism and gut microbiota are the two main reasons. However, the potential mechanisms still need to be elucidated. In this review, we mainly discussed how bile acid metabolism, gut microbiota, and the interaction between the two factors influence the development of CRC. Subsequently, we summarized the underlying mechanisms of the alterations in bile acid metabolism after cholecystectomy including cellular level, molecular level, and signaling pathways. The potential mechanisms of the alterations on gut microbiota contain an imbalance of bile acid metabolism, cellular immune abnormality, acid-base imbalance, activation of cancer-related pathways, and induction of toxin, inflammation, and oxidative stress.

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