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二氢丹参酮通过抑制JAK2/STAT3信号通路抑制肝细胞癌

Dihydrotanshinone Inhibits Hepatocellular Carcinoma by Suppressing the JAK2/STAT3 Pathway.

作者信息

Hu Xue, Jiao Fangzhou, Zhang Lan, Jiang Yingan

机构信息

Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Pharmacol. 2021 Apr 29;12:654986. doi: 10.3389/fphar.2021.654986. eCollection 2021.

Abstract

Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death. Most (75-85%) primary liver cancers occurring worldwide are hepatocellular carcinoma (HCC). The development of resistance and other drug related side effects are the prime reasons for the failure of treatment. Therefore, developing high-efficacy and low-toxicity natural anticancer agents is greatly needed in the treatment of HCC. Dihydrotanshinone (DHTS) is widely used for promoting blood circulation and antitumor. The aim of the present study was to investigate the effect and mechanism of DHTS-induced apoptosis of HCC, both and . We found that DHTS inhibited the growth of several HCC cells (HCCLM3, SMMC7721, Hep3B and HepG2). DHTS induced the apoptosis of SMMC7721 cells. Immunofluorescence results have showed that DHTS decreased STAT3 nuclear translocation. Moreover, Western blot results have demonstrated that DHTS suppressed the activation of JAK2/STAT3 signaling pathway. In addition, xenograft results have showed that DHTS suppressed tumor growth of SMMC7721 cells by inhibiting the p-STAT3. Thus, we demonstrated that DHTS could inhibit HCC by suppressing the JAK2/STAT3 pathway. DHTS has potential to be a chemotherapeutic agent in HCC and merits further clinical investigation.

摘要

肝癌是第六大最常被诊断出的癌症,也是癌症死亡的第四大主要原因。全球范围内发生的大多数原发性肝癌(75 - 85%)为肝细胞癌(HCC)。耐药性的产生以及其他与药物相关的副作用是治疗失败的主要原因。因此,在肝癌治疗中非常需要开发高效低毒的天然抗癌药物。二氢丹参酮(DHTS)被广泛用于促进血液循环和抗肿瘤。本研究的目的是研究DHTS诱导肝癌细胞凋亡的作用及机制,包括体内和体外实验。我们发现DHTS抑制了几种肝癌细胞(HCCLM3、SMMC7721、Hep3B和HepG2)的生长。DHTS诱导了SMMC7721细胞凋亡。免疫荧光结果显示DHTS减少了STAT3的核转位。此外,蛋白质印迹结果表明DHTS抑制了JAK2/STAT3信号通路的激活。另外,异种移植结果显示DHTS通过抑制p-STAT3抑制了SMMC7721细胞的肿瘤生长。因此,我们证明DHTS可通过抑制JAK2/STAT3通路抑制肝癌。DHTS有潜力成为肝癌的化疗药物,值得进一步的临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35d/8117156/bca581a52d7d/fphar-12-654986-g001.jpg

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