Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

肌少症对老年肝癌术后恢复及预后的影响

目的:肌少症对老年肝癌术后恢复及预后的影响。方法:选取2015年1月至2017年12月收治的114例老年肝癌，根据有无合并肌少症，分为肌少症组（n=35）和非肌少症组（n=79）。比较两组患者的术后恢复及生存情况。结果:肌少症组总并发症发生率、住院时间和30 d再入院率均高于对照组，差异均有统计学意义（P＜0.05）。肌少症组中位生存时间为25.9个月，1年、2年、3年累积总生存率为74.3%、51.1%、24.5%，而非肌少症组中位生存时间为35.7个月，1年、2年、3年累积总生存率为87.3%、75.6%、49.4%，差异有统计学意义（P=0.004）。单因素分析结果显示，老年肝癌术后预后与Charlson合并症指数（CCI）、肌少症、巴塞罗那分期（BCLC）、甲胎蛋白、肿瘤大小、肿瘤个数、肿瘤分化程度、微血管侵犯（MVI）相关（P＜0.05）。Cox多因素分析结果显示，CCI、肌少症、BCLC分期、肿瘤个数、MVI是老年肝癌术后预后的独立危险因素（P＜0.05）。结论:肌少症会增加老年肝癌患者术后并发症发生率，延长住院时间，影响术后恢复，同时也会降低总生存率。