Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin.
Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin.
复制标题
紫草素通过抑制 C-MYC 和 PI3K/AKT/mTOR 通路在伯基特淋巴瘤中发挥抗肿瘤活性，并与阿霉素协同作用
DOI：
10.1038/s41598-018-21570-z
复制
发表时间：
2018-02-20
影响因子：
4.6
通讯作者：
Tong X
中科院分区：
文献类型：
--
作者：
Ni F;Huang X;Chen Z;Qian W;Tong X
伯基特淋巴瘤（BL）是一种高度侵袭性的恶性肿瘤，其分子特征是C-MYC原癌基因失调。近年来，研究证实磷脂酰肌醇-3-激酶（PI 3 K）通路的激活是BL B细胞恶性转化的关键因素。尽管高强度化疗方案治疗成人BL的结果更好，但60岁以上患者的总体生存率仍然令人沮丧。紫草素是从中草药中提取的一种天然萘醌类化合物，在一系列人类肿瘤中具有诱导细胞死亡的作用。本研究旨在探讨紫草素对BL的治疗作用及其分子机制。紫草素抑制BL细胞增殖并诱导caspase依赖性凋亡。抑制C-MYC和PI 3 K/AKT/mTOR通路在SHK诱导BL细胞凋亡中起重要作用。此外，紫草素在体外增强阿霉素诱导的细胞生长抑制和凋亡。此外，紫草素对BL皮下移植瘤模型的生长有明显的抑制作用。重要的是，我们没有发现紫草素对小鼠肝功能的影响。总之，这些数据表明，紫草素可能是一个令人鼓舞的化疗药物在BL的临床治疗。
Burkitt’s lymphoma (BL) is a highly aggressive malignancy molecularly characterized by deregulation of the C-MYC proto-oncogene. Recently, it has been confirmed that phosphatidylinositol-3-kinase (PI3K) pathway activation is a crucial element in the malignant transformation of the B cells in BL. Despite the better outcome of adults with BL treated with high-intensity chemotherapy regimens, the overall survival rate for patients older than 60 years remains dismal. Shikonin, a natural naphthoquinone derived from Chinese herbal medicine plant, has the potential to induce cell death in a series of human cancer. In the present study, we investigated the effect and molecular mechanisms of Shikonin in treatment with BL. Shikonin suppressed cellular proliferation and induced caspase-dependent apoptosis in BL cells. Inhibition of C-MYC and suppression of PI3K/AKT/mTOR pathway played critical roles in SHK-induced apoptosis in BL both in vitro and in vivo. Besides, Shikonin potentiated doxorubicin-induced growth inhibition and apoptosis in vitro. Furthermore, the growth of a subcutaneous xenograft tumor model of BL was significantly inhibited by shikonin. Importantly, we did not find the effect of shikonin on liver function in mice. In summary, these data suggest that shikonin may be an encouraging chemotherapeutic agent in the clinical treatment of BL.
登录
查看更多内容
影响因子：
28.5
作者：
Abruzzese MP;Bilotta MT;Fionda C;Zingoni A;Soriani A;Vulpis E;Borrelli C;Zitti B;Petrucci MT;Ricciardi MR;Molfetta R;Paolini R;Santoni A;Cippitelli M
通讯作者：
Cippitelli M
影响因子：
28.5
作者：
Liu J;Pan C;Guo L;Wu M;Guo J;Peng S;Wu Q;Zuo Q
通讯作者：
Zuo Q
影响因子：
64.5
作者：
Delmore JE;Issa GC;Lemieux ME;Rahl PB;Shi J;Jacobs HM;Kastritis E;Gilpatrick T;Paranal RM;Qi J;Chesi M;Schinzel AC;McKeown MR;Heffernan TP;Vakoc CR;Bergsagel PL;Ghobrial IM;Richardson PG;Young RA;Hahn WC;Anderson KC;Kung AL;Bradner JE;Mitsiades CS
通讯作者：
Mitsiades CS
影响因子：
44.1
作者：
Mao, Xin;Yu, Chun Rong;Li, Wen Xin
通讯作者：
Li, Wen Xin
影响因子：
6.5
作者：
Goldman S;Smith L;Galardy P;Perkins SL;Frazer JK;Sanger W;Anderson JR;Gross TG;Weinstein H;Harrison L;Shiramizu B;Barth M;Cairo MS
通讯作者：
Cairo MS