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Abstract As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.

Summary: Background: Gastric neuroendocrine carcinomas (G-NECs) are rare. This study aimed to explore the feasibility and clinical efficacy of laparoscopic surgery in patients with advanced G-NECs. Methods: The clinicopathological data of 175 G-NECs patients who underwent radical gastrectomy in a high-volume centre were collected. One hundred fifty-one cases with advanced G-NECs (laparoscopic gastrectomy [LG] = 30, open gastrectomy [OG] = 121) were finally selected for comparison of the short-term outcomes and oncologic efficacy. Results: In the postoperative recovery, when comparing the OG group, the time to ambulation (3.2 d vs. 2.6 d, respectively, p = 0.049), the time to first flatus (4.1 d vs. 3.6 d, respectively, p = 0.050), the time to first soft diet (7.9 d vs. 6.7 d, respectively, p = 0.007), and the postoperative hospital stay (13.1 d vs. 11.4 d, respectively, p = 0.047) of the LG group were shorter. There was no significant difference in the postoperative complication rates between the OG and LG groups (19.8% vs. 23.3%, p = 0.671). The 3-year overall survival (OS) rate was 57.0% in the OG group and 64.4% in the LG group (p = 0.349). The 3-year disease-free survival (DFS) rate was 51.7% in the OG group and 57.4% in the LG group (p = 0.357). There was no significant difference in the 3-year OS and DFS rates between the LG and OG groups at each stage. The recurrence rate was 35.5% in the OG group and 33.0% in the LG group (p = 0.821). Conclusions: The short-term outcomes and oncologic efficacy of laparoscopic gastrectomy and open gastrectomy for advanced G-NECs are comparable. Keywords: Gastric neuroendocrine carcinomas, Open surgery, Laparoscopic surgery, Short-term outcome, Oncologic efficacy

Gastric cancer seriously affects human health and research on gastric cancer is attracting more and more attentions. In recent years, molecular targets have become the research focus. Accumulating evidence indicates that miR-450a-5p plays a critical role in cancer progression. However, the biological role of miR-450a-5p in gastric carcinogenesis remains largely unknown. In this study, we explore the effects and mechanisms of miR-450a-5p on the development and progression of gastric cancer. We used gain-of-function approaches to investigate the role of miR-450a-5p on gastric cancer cell proliferation, migration, invasion, and apoptosis using biological and molecular techniques including real-time quantitative PCR (RT-qPCR), CCK-8, colony formation, flow cytometry, Western blot, wound healing, transwell chamber, dual luciferase reporter, and tumor xenograft mouse model. We found that gastric cancer cells have low expression of miR-450a-5p and overexpression of miR-450a-5p inhibited gastric cancer cell proliferation, migration and invasion, and induced apoptosis in vitro. Moreover, we demonstrated that ectopic expression of miR-450a-5p inhibited gastric cancer growth in vivo. At the molecular level, overexpression of miR-450a-5p significantly increased the expression of pro-apoptotic proteins, including caspase-3, caspase-9, and Bax, and inhibited the expression of anti-apoptotic protein Bcl-2. Luciferase reporter experiment suggested that camp response element binding protein 1 (CREB1) had a negative correlation with miR-450a-5p expression, and knockdown of CREB1 alleviated gastric cancer growth. Furthermore, we also found that miR-450a-5p inhibited the activation of AKT/GSK-3β signaling pathway to inhibit the progression of gastric cancer. Collectively, miR-450a-5p repressed gastric cancer cell proliferation, migration and invasion and induced apoptosis through targeting CREB1 by inhibiting AKT/GSK-3β signaling pathway. MiR-450a-5p could be a novel molecular target for the treatment of gastric cancer.