Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway

Nasopharyngeal carcinoma(NPC)is the third most common malignancy with a high recurrence and metastasis rate in South China.Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects.Maackiain(MA)is a type of flavonoid that was first isolated from leguminous plants,and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as antiinflammatory effects.In this study,we demonstrated that MA inhibited proliferation,arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo.The expression of the related proteins associated with these processes were consistent with the above effects.Moreover,transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells.Therefore,the effects of MA and an activator of this pathway,tertiary butylhydroquinone(TBHQ),alone or combination,were investigated.The results showed TBHQ neutralized the inhibitory effects of MA.These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

金银花总皂苷对甲状腺癌TPC-1细胞增殖、侵袭、凋亡及SHP2/Ras/MAPK通路的影响

目的:探讨金银花总皂苷对甲状腺癌TPC-1细胞增殖、侵袭、凋亡及SHP2/Ras/MAPK通路的影响。方法:设甲状腺癌TPC-1细胞组、5-氟尿嘧啶组(500μmol·ml^(-1))、金银花总皂苷低和高剂量组(500μmol·ml^(-1)、1000μmol·ml^(-1)),以上各组每孔设6个平行样,培养72h。试验结束后,应用CCK-8试剂盒测定细胞增殖水平,Transwell室测定细胞侵袭水平,流式细胞仪测定细胞凋亡水平,RT-PCR法及蛋白印迹法测定细胞SHP2、Ras、MAPK mRNA及蛋白水平。结果:与甲状腺癌TPC-1细胞组比较,5-氟尿嘧啶组、金银花总皂苷低、高剂量组OD值、存活率、穿膜数、侵袭距离、SHP2、Ras、MAPK mRNA和蛋白表达水平降低,凋亡率升高(P<0.05)。与5-氟尿嘧啶组比较,金银花总皂苷低剂量组OD值、存活率、穿膜数、侵袭距离、SHP2、Ras、MAPK mRNA和蛋白表达水平升高,凋亡率降低(P<0.05),金银花总皂苷高剂量组OD值、存活率、凋亡率、穿膜数、侵袭距离、SHP2、Ras、MAPK mRNA和蛋白表达水平无明显变化(P>0.05)。与金银花总皂苷低剂量组比较,金银花总皂苷高剂量组OD值、存活率、穿膜数、侵袭距离、SHP2、Ras、MAPK mRNA和蛋白表达水平降低,凋亡率升高(P<0.05)。结论:金银花总皂苷能抑制甲状腺癌细胞的增殖、侵袭并增强其凋亡,其机制可能与金银花总皂苷抑制SHP2/Ras/MAPK信号通路的激活有关。