3D打印制备不同重量比例的n-HA/PLA/PVA复合膜性能比较

目的:通过3D打印的方法制备的不同重量比例的纳米羟基磷灰石/聚乳酸/聚乙烯醇(n-HA/PLA/PVA)复合膜,并对其相关性能检测。方法:采用3D打印技术制备不同重量比例的n-HA/PLA/PVA复合膜,分别为PLA/PVA复合膜、15%n-HA/PLA/PVA复合膜、50%n-HA/PLA/PVA复合膜、75%n-HA/PLA/PVA复合膜。扫描电镜下观察各组膜形态,对其力学性能、细胞毒性及动物实验相应指标进行检测。结果:扫描电镜下观察,n-HA/PLA/PVA复合膜呈现三维网状结构,各材料间相互结合,孔隙分布不均,大小不一。随着n-HA质量浓度的提高,电镜下见各材料间孔隙逐渐减小,形成结构均匀的复合膜。力学性能及吸水率检测中,随着nHA含量的增加,n-HA/PLA/PVA复合膜的拉伸强度及吸水率呈下降趋势;细胞毒性检测,不同比例复合膜的细胞增殖率无明显差别,无细胞毒性。动物实验测量牙周菌斑指数及龈沟出血指数未发现不同比例n-HA/PLA/PVA复合膜有统计学差异。结论:3D打印不同比例的n-HA/PLA/PVA复合膜具有良好的物理性能和细胞生物相容性,n-HA比例更高的复合膜可能具有更好的物理性能及良好的生物相容性。     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

蓝莓花青素对人胃腺癌BGC-823细胞增殖、侵袭的影响及机制研究

目的:探讨蓝莓花青素(BA)对人胃腺癌BGC-823细胞增殖、侵袭的影响及相关机制。方法:低、中、高剂量实验组与对照组人胃腺癌BGC-823细胞分别以25、50、100μg/mL BA与等量生理盐水处理,分别处理12 h、24 h、48 h。采用噻唑蓝(MTT)与流式细胞仪检测人胃腺癌BGC-823细胞增殖与凋亡;采用Transwell小室实验与免疫细胞化学法检测人胃腺癌BGC-823细胞侵袭与P53、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。结果:干预48 h时,对照组、低、中、高剂量实验组人胃腺癌BGC-823细胞P53与Caspase-3蛋白阳性细胞百分比分别为(11.12±1.01)%,(24.31±2.18)%,(47.56±2.91)%,(66.49±5.14)%与(15.04±1.23)%,(28.22±3.09)%,(69.36±5.42)%,(86.52±6.15)%。实验组胃腺癌BGC-823细胞增殖抑制率随BA浓度增大而逐渐升高;与对照组比较,低、中、高剂量实验组人胃腺癌BGC-823细胞凋亡率、P53与Caspase-3蛋白阳性细胞百分比均显著升高,侵袭率降低,呈浓度依赖性(均P0.05)。结论:BA可有效抑制胃腺癌BGC-823细胞增殖,诱导其凋亡,并降低侵袭能力,其机制可能与上调P53与Caspase-3蛋白表达有关。     

MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.