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

Xue Hu,Yingan Jiang,Lan Zhang,Fangzhou Jiao

doi:10.3389/fphar.2021.654986

Xue Hu, Yingan Jiang + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2021.654986

Copy DOI

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 in vitro and in vivo. 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 in vivo 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.

Highlights

Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death (Huang et al, 2020)
We evaluated the antitumor effects of DHTS on different hepatocellular carcinoma (HCC) tumor cells
Further experiments showed that DHTS can target STAT3 and play a role in antitumor activity

Summary

Introduction

Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death (Huang et al, 2020). Most (75–85%) primary liver cancers occurring worldwide are hepatocellular carcinoma (HCC) (Huang et al, 2020). HCC is one of the most common malignancies worldwide, in many Asian and Eastern Africa (Kutluet et al, 2018; Yang et al, 2019; Huang et al, 2020). 40–70% of patients relapse within 5 years of removal of HCC (Wen et al, 2018). Systemic chemotherapy is another possible common therapy. Developing high-efficacy and low-toxicity natural anticancer agents is greatly needed in the treatment of HCC

Objectives

Methods

Results

Conclusion