Prostate cancer (PC) is one of the most common malignant tumors in man. Peimine (PM) is a bioactive substance isolated from Fritillaria. Previous studies have shown that PM could inhibit the occurrence of a variety of cancers. However, the roles of PM in PC and its related mechanism have not been elucidated. Calcium (Ca2+) is an important intracellular messenger involved in a variety of cell processes. In this study, we found that the appropriate doses of PM (2.5, 5, and 10 μM) significantly inhibited the growth of PC cells (DU‐145, LNCap, and PC‐3), but has no significant effect on normal prostate cells (RWPE‐1). In addition, PM treatment inhibited the invasion and migration of PC‐3 cells and blocked the epithelial‐mesenchymal transition process. These effects were exhibited a dose‐dependent manner. Furthermore, the current results also showed that PM treatment significantly increased the Ca2+ concentration, the increased Ca2+ promoted the phosphorylation of Ca2+/calmodulin‐dependent protein kinase II (CaMKII) and c‐Jun N‐terminal kinase (JNK), further inhibited the growth and invasion of PC‐3 cells, and induced its apoptosis. Ca2+ chelator BAPTA‐AM (1 μM) could counteract the increase of intracellular Ca2+ concentration. Similarly, JNK pathway inhibitor SP600125 (10 μM) also inhibited cell growth and invasion and induced apoptosis. In addition, experiments in nude mice showed that PM inhibited tumor formation through Ca2+/CaMKII/JNK signaling pathway. In conclusion, our results show that PM inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+/CaMKII/JNK pathway.

BACKGROUND: Long noncoding RNA (lncRNA) are critical regulators of tumor progression. OBJECTIVE: To determine how the lncRNA membrane associated guanylate kinase, WW and PDZ domain-containing 2 (MAG12) antisense RNA 3 (MAGI2-AS3) and the phosphatase and tensin homolog (PTEN) gene function in regulating bladder cancer (Bca) progression. METHODS: Total RNA from 80 and 30 paired resected Bca and para-cancerous tissues from patients with confirmed Bca was sequentially extracted, quantified, purified, and reverse transcribed using RT-PCR. A library was constructed and sequenced. Four Bca cell lines and a normal urothelial cell line were transfected with lentiviral plasmids, and cell migration and invasion were assayed in vitro. An orthotopic mouse model of Bca was created for in vivo studies. RESULTS: MAGI2-AS3 expression was significantly downregulated in Bca, compared with normal tissues, and negatively associated with tumor stage and a poor prognosis. MAGI2-AS3 and its sense RNA MAGI2 showed significant and positive correlation. The expression of MAGI2 and its downstream gene, PTEN, increased in Bca cells overexpressing MAGI2-AS3, and interference by MAGI2 expression reversed the migration and invasion inhibited by MAGI2-AS3 overexpression. CONCLUSION: MAGI2-AS3 overexpression inhibited Bca cell progression by regulating the MAGI2/PTEN/epithelial-mesenchymal transition, offering novel insights into the mechanism of Bca progression.

Increasing life expectancy imposes big challenges to the global health of the male population, because some disorders, such as tumours, tend to progress with age (Bell et al., 2015). Among them, prostate cancer (PCa) is a leading cause of cancer-associated mortality among men, specifically in Western countries; the lowest rates of this cancer are seen in Africa and Asia. PCa has the highest heritability, accounting for almost 10% of all new male tumours. More than 650,000 men worldwide are diagnosed with PCa annually (Fitzpatrick et al., 2009). In addition to family history and genetic factors, well-established risk factors for PCa include Lynch syndrome, country of origin, age and race/ethnicity (Grönberg, 2003; Teoh et al., 2019). Today, PCa is diagnosed based on the measurement of serum prostate-specific antigen (PSA), also known as DRE (Misawa et al., 2017). PC3 is a grade IV PCa cell line that does not respond to fibroblast growth factors (FGF), androgens or glucocorticoids and has potential metastatic activity. It is useful in studying curative interventions in progressive PCa cells (Ashtiani et al., 2017). Understanding the molecular mechanisms correlated with PCa development and progression is pivotal, where long noncoding RNAs (lncRNAs) are hopeful candidates in assessing PCa initiation and tumorigenesis. Only a small portion of transcripts are translated into proteins, while the majority of them are noncoding RNAs (ncRNAs) (Bray