Background To observe the anti-proliferative effects and molecular mechanisms of traditional Chinese medicine prescriptions Xi-Huang pellet （XHP） on human breast cancer cell line SKBR3. Materials and Methods： Huma...Background To observe the anti-proliferative effects and molecular mechanisms of traditional Chinese medicine prescriptions Xi-Huang pellet （XHP） on human breast cancer cell line SKBR3. Materials and Methods： Human breast cancer cell line SKBR3 was cultured. Trypan blue exclusion assay was used to investigate the anti-proliferative effects of medicine. The rates of the cell cycle were measured by ^ow cytometry （FCM）. The impacts of medicine on the protein expression were detected by Enzyme-linked immunosorbent assay （ELISA）. RNA extraction and real-time PCR were used to observe the change of RNA expression. Results： Myrrh, XHP and XHP combined 5-FU could inhibit cellproliferation and arrest SKBR3 cells at S phases. XHP combined 5-FU resulted in a significant increase of intracellular p21WAF1/CiP1 content in SKBR3 cells. XHP and XHP combined 5-FU led to a decrease of mRNA expression on cyclin A2, cyclin D1 and cyclin E in SKBR3 cells. Conclusions： XHP inhibits the proliferation of breast cancer SKBR3 cells via a significantly change of cyclins expression and p21WAF1/CIP1 pathway. 5-FU significantly enhanced the inhibitory effects of XHP on SKBR3 cells.展开更多
目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微...目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微畸形和进行性异位骨化等临床表现,结合骨骼系统放射线检查、骨ECT和相关血液生化检查进行临床诊断。采集患者、患者父母和60位正常人外周血,提取基因组DNA,对ACVR1基因全部外显子进行聚合酶链反应(polymerase chain reaction,PCR)扩增和序列分析;对突变后的蛋白质结构进行分子模拟以便评估其突变后的功能改变。结果:患者具有非典型的临床表现:先天性大踇趾轻微畸形和进行性非经典顺序的异位骨化,其父母无FOP相关临床表现。患者的ACVR1第5外显子存在c.774 G>C(R258S)杂合突变,而其父母和正常对照组均无此杂合突变。此外,患者和所有正常人都存在c.690 G>A(E230E),此为无意义突变。三维蛋白质分子模拟发现R258与高度保守的甘氨酸-丝氨酸(glycine-serine,GS)活化区邻近,该突变可能导致ACVR1与ACVR1的抑制蛋白FK506结合蛋白12(FK506 binding protein 12,FKBP12)结合的亲和力降低,进而对ACVR1抑制作用降低。结论:典型FOP均在ACVR1之GS区发生突变,而本例FOP在ACVR1激酶区发生突变,这可能是该患者在临床表现呈非典型的原因。该结果有助于我们更好地去理解FOP表型和基因型之间的关系。展开更多
基金This work was supported by grants from the National Science Foundation of China （No. 81173376） and New Century Excellent Talent （NCET-11-1068）.
文摘Background To observe the anti-proliferative effects and molecular mechanisms of traditional Chinese medicine prescriptions Xi-Huang pellet （XHP） on human breast cancer cell line SKBR3. Materials and Methods： Human breast cancer cell line SKBR3 was cultured. Trypan blue exclusion assay was used to investigate the anti-proliferative effects of medicine. The rates of the cell cycle were measured by ^ow cytometry （FCM）. The impacts of medicine on the protein expression were detected by Enzyme-linked immunosorbent assay （ELISA）. RNA extraction and real-time PCR were used to observe the change of RNA expression. Results： Myrrh, XHP and XHP combined 5-FU could inhibit cellproliferation and arrest SKBR3 cells at S phases. XHP combined 5-FU resulted in a significant increase of intracellular p21WAF1/CiP1 content in SKBR3 cells. XHP and XHP combined 5-FU led to a decrease of mRNA expression on cyclin A2, cyclin D1 and cyclin E in SKBR3 cells. Conclusions： XHP inhibits the proliferation of breast cancer SKBR3 cells via a significantly change of cyclins expression and p21WAF1/CIP1 pathway. 5-FU significantly enhanced the inhibitory effects of XHP on SKBR3 cells.
文摘目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微畸形和进行性异位骨化等临床表现,结合骨骼系统放射线检查、骨ECT和相关血液生化检查进行临床诊断。采集患者、患者父母和60位正常人外周血,提取基因组DNA,对ACVR1基因全部外显子进行聚合酶链反应(polymerase chain reaction,PCR)扩增和序列分析;对突变后的蛋白质结构进行分子模拟以便评估其突变后的功能改变。结果:患者具有非典型的临床表现:先天性大踇趾轻微畸形和进行性非经典顺序的异位骨化,其父母无FOP相关临床表现。患者的ACVR1第5外显子存在c.774 G>C(R258S)杂合突变,而其父母和正常对照组均无此杂合突变。此外,患者和所有正常人都存在c.690 G>A(E230E),此为无意义突变。三维蛋白质分子模拟发现R258与高度保守的甘氨酸-丝氨酸(glycine-serine,GS)活化区邻近,该突变可能导致ACVR1与ACVR1的抑制蛋白FK506结合蛋白12(FK506 binding protein 12,FKBP12)结合的亲和力降低,进而对ACVR1抑制作用降低。结论:典型FOP均在ACVR1之GS区发生突变,而本例FOP在ACVR1激酶区发生突变,这可能是该患者在临床表现呈非典型的原因。该结果有助于我们更好地去理解FOP表型和基因型之间的关系。
