Ginsenoside Rg3 plus Artesunate Overcomes Sorafenib Resistance in Hepatoma by Inhibiting Src/STAT3 Signaling and Modulating ROS/STAT3 Signaling.

Ying-Jie Chen, Jia-Ying Wu, Yu-Yi Deng, Xiu-Qiong Fu, Ying Wu, Xiao-Qi Wang, Amy Sze-man Li, Lut-Yi Wong, Zhi-Ling Yu*

*Corresponding author for this work

Research output: Contribution to conferenceConference abstractpeer-review

Abstract

Sorafenib is effective in treating hepatoma, but most patients develop resistance to it STAT3 signaling has been implicated in sorafenib resistance. Aitesunate (ART) and 2(XR}-ginsenoside Rg3 (Rg3) Eave anh-Eep3toma effects and can inhibit STATS signaling in cancer cells. This study-aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcaning sorafenb resistance, and to explore the involvement of STAT3 signaling in these effects. Sorafemb-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro antihepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assay and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was measured by DCF-DA staining. Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Fuifeesmae. over-activation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART‘s inhibitory effects on STAT3 activation in HepG2-SR cells. In summary, Rg3-plus-ART overcomes sorafenib resistance in experimental models and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafemb-resistant hepatoma.
Original languageEnglish
Pages280
Number of pages1
Publication statusPublished - 4 Nov 2022
EventThe 10th Biennial Meeting of Society for Free Radical Research Asia, SFRR-Asia 2022 - Seoul National University, Seoul, Korea, Republic of
Duration: 4 Nov 20226 Nov 2022
http://sfrrj.umin.jp/asia/en_Biennial_Meeting.htm

Conference

ConferenceThe 10th Biennial Meeting of Society for Free Radical Research Asia, SFRR-Asia 2022
Country/TerritoryKorea, Republic of
CitySeoul
Period4/11/226/11/22
Internet address

User-Defined Keywords

  • Sorafenib resistance Hepatoma
  • Src/STAT3 signaling
  • ROS/STAT3 signaling
  • Ginsenoside Rg3
  • Artesunate

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