Naringin inhibits cisplatin resistance of ovarian cancer cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Background: Resistance to cisplatin (DDP) in patients with ovarian cancer (OC) poses a great challenge to improving the quality of life of patients. Past reports have revealed that naringin can induce apoptosis of OC cells and delay the occurrence of drug resistance in OC cells. However, the molecular role by which naringin inhibits DDP resistance in OC has not been definitively proven by researchers. The objective of this study is to investigate the effect of naringin on DDP resistance in OC cells and the specific mechanism of naringin mediating autophagy. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were selected to evaluate the role of naringin or DDP on the proliferation and apoptosis of human OC cells (SKOV3/A2780). The protein levels of Sequestosome 1 (SQSTM1/p62, hereinafter referred to as p62), microtubule-associated protein 1 light chain 3 (LC3), transforming growth factor-ß2 (TGF-ß2) and SMAD family member 2 (smad2) were detected with Western blotting assay. Immunofluorescence assay was also used to evaluate the level of LC3 in different groups of cells. Besides, functional analyses were performed in vivo. Results: Naringin was shown to promote DDP sensitivity and apoptosis of human OC DDP-resistant cell line (SKOV3/A2780-DDP cells). Significantly increased p62 expression and reduced LC3 expression were found in naringin-treated cells. The autophagy agonist, rapamycin, reversed the effect of naringin on the resistance of SKOV3-DDP cells to DDP. Naringin inhibited levels of TGF-ß2/smad2 pathway-related proteins, and regulated autophagy in SKOV3-DDP cells. In vivo experiments demonstrated that injection of naringin inhibited DDP resistance and autophagy in mice xenograft model. Conclusions: In summary, naringin inhibits DDP resistance in OC cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Phellinus igniarius polysaccharides induced mitochondrial apoptosis of hepatic carcinoma by enhancing reactive oxygen species-mediated AKT/p53 signalling pathways.

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5 ± 1.6% neutral carbohydrates. PIP consists of glucose, galactose, mannose, xylose, D-fructose, L-guluronic acid, glucosamine hydrochloride, rhamnose, arabinose and D-mannoturonic acid. PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway.

Causes of Death Following Gastric Cancer Diagnosis: A Population-Based Analysis.

BACKGROUND Causes of death (CODs) in patients with gastric cancer (GC) need to be studied. We examined the cancer-specific and non-cancer deaths among patients diagnosed with GC from 1975 to 2019. MATERIAL AND METHODS We obtained medical records from the Surveillance, Epidemiology, and End Results (SEER) database. We used SEER*Stat software to calculate standardized mortality ratios (SMRs) for specific CODs and performed a competing risk analysis to evaluate the cumulative mortality of specific CODs. RESULTS The final study cohort included 42 813 patients with GC, with a mean age at diagnosis of 67.7 years. As the end of 2021, a total of 36 924 (86.2%) patients died. Of these deaths, 24 625 (66.7%) were from GC, 6513 (17.6%) were from other types of cancers, and 5786 (15.7%) were from non-cancer causes. The most prevalent non-cancer CODs were heart diseases (2104; 5.7%), cerebrovascular diseases (501; 1.4%), and pneumonia/influenza (335; 0.9%). Among patients who survived over 5 years, non-cancer causes surpassed GC as the main CODs. Patients with GC had a higher risk of dying from many non-cancer causes than expected in the general population, particularly from suicide (SMR, 3.03; 95% CI, 2.35-3.85) and septicemia (SMR, 2.93; 95% CI, 2.51-3.4). The competing risk analysis showed that the cumulative mortality of GC gradually declined with a more recent diagnosis. CONCLUSIONS Although GC was the leading COD among patients with GC, non-cancer CODs accounted for a substantial number of deaths. These findings provide useful guidance on potential death risks among patients with GC.

Effects of lncRNA ANRIL-knockdown on the proliferation, apoptosis and cell cycle of gastric cancer cells.

Gastric cancer is one of the most common types of malignant tumor of the gastrointestinal tract worldwide. Cisplatin (DDP) is a commonly used chemotherapeutic drug in the clinic; however, the resistance of gastric cancer cells to DDP limits its efficacy. In the present study, drug-resistant gastric cancer cell lines were constructed using the stepwise continuous selection method, and the relative expression levels of long non-coding RNA (lncRNA) CDKN2B antisense RNA 1 (ANRIL) and microRNA (miR)-181a-5p were detected using reverse transcription-quantitative PCR. The knockdown of lncRNA ANRIL and miR-181a-5p expression was performed by transfection with shRNA-ANRIL and an miR-181a-5p inhibitor, respectively. Cellular proliferation and sensitivity to DDP were assessed using Cell Counting Kit-8 analysis. Cell apoptosis and cell cycle distribution were assessed using flow cytometry and western blotting. The binding relationships between ANRIL, miR-181a-5p and cyclin G1 (CCNG1) were verified using a dual luciferase reporter assay. The results revealed that the expression levels of miR-181a-5p were downregulated in all drug-resistant cell lines. ANRIL-knockdown inhibited cellular proliferation, and promoted apoptosis and cell cycle arrest; however, following the knockdown of miR-181a-5p, the inhibition of cell cycle arrest was alleviated. Notably, miR-181a-5p, ANRIL and CCNG1 were found to have targeting relationships. In conclusion, the findings of the present study suggested that knocking down the expression of ANRIL inhibited cellular proliferation, and promoted apoptosis and cell cycle arrest. Furthermore, its downstream target, miR-181a-5p, inhibited the proliferation of drug-resistant cells and enhanced their sensitivity to DDP.