Enzalutamide and olaparib synergistically suppress castration-resistant prostate cancer progression by promoting apoptosis through inhibiting nonhomologous end joining pathway.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

Massive migration promotes the early spread of COVID-19 in China: a study based on a scale-free network.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic met coincidentally with massive migration before Lunar New Year in China in early 2020. This study is to investigate the relationship between the massive migration and the coronavirus disease 2019 (COVID-19) epidemic in China. METHODS: The epidemic data between January 25th and February 15th and migration data between Jan 1st and Jan 24th were collected from the official websites. Using the R package WGCNA, we established a scale-free network of the selected cities. Correlation analysis was applied to describe the correlation between the Spring Migration and COVID-19 epidemic. RESULTS: The epidemic seriousness in Hubei (except the city of Wuhan) was closely correlated with the migration from Wuhan between January 10 and January 24, 2020. The epidemic seriousness in the other provinces, municipalities and autonomous regions was largely affected by the immigration from Wuhan. By establishing a scale-free network of the regions, we divided the regions into two modules. The regions in the brown module consisted of three municipalities, nine provincial capitals and other 12 cities. The COVID-19 epidemics in these regions were more likely to be aggravated by migration. CONCLUSIONS: The migration from Wuhan could partly explain the epidemic seriousness in Hubei Province and other regions. The scale-free network we have established can better evaluate the epidemic. Three municipalities (Beijing, Shanghai and Tianjin), eight provincial capitals (including Nanjing, Changsha et al.) and 12 other cities (including Qingdao, Zhongshan, Shenzhen et al.) were hub cities in the spread of COVID-19 in China.