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 language | English |
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Pages | 280 |
Number of pages | 1 |
Publication status | Published - 4 Nov 2022 |
Event | The 10th Biennial Meeting of Society for Free Radical Research Asia, SFRR-Asia 2022 - Seoul National University, Seoul, Korea, Republic of Duration: 4 Nov 2022 → 6 Nov 2022 http://sfrrj.umin.jp/asia/en_Biennial_Meeting.htm |
Conference
Conference | The 10th Biennial Meeting of Society for Free Radical Research Asia, SFRR-Asia 2022 |
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Country/Territory | Korea, Republic of |
City | Seoul |
Period | 4/11/22 → 6/11/22 |
Internet address |
User-Defined Keywords
- Sorafenib resistance Hepatoma
- Src/STAT3 signaling
- ROS/STAT3 signaling
- Ginsenoside Rg3
- Artesunate